Journal articles on the topic 'Chemotherapy-induced febrile neutropenia; cancer patients; prognostic model'
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Chantharakhit, Chaichana, and Nantapa Sujaritvanichpong. "Pretreatment Absolute Neutrophil-to-Lymphocyte Ratio (NLR) Predict the Risk for Febrile Neutropenia in the First Cycle Adjuvant Chemotherapy for Breast Cancer." Asian Pacific Journal of Cancer Biology 5, no. 3 (September 15, 2020): 81–87. http://dx.doi.org/10.31557/apjcb.2020.5.3.81-87.
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Background: Chemotherapy-induced febrile neutropenia (FN) is a condition affecting mortality and morbidity. The records show that absolute neutrophil-to-lymphocyte ratio (NLR) is associated with the cancer prognosis and reflects the immune response system on the infection. It can be used as an independent prognostic biomarker and predictive marker in patients with chronic inflammatory diseases, cardiovascular diseases, or malignancies. Therefore, we have been conducted on using absolute NLR to predict FN in a patient with breast cancer who has adjuvant chemotherapy. Materials and Methods: The authors retrospectively evaluated the pretreatment absolute NLR of patients with early stage breast cancer who had adjuvant chemotherapy. Then, the relationship to FN was analyzed by using multivariate logistic regression analysis. Results: We conducted a retrospective analysis of 339 patients where 21 patients had developed FN (6.19%). The multivariate logistic regression analysis results indicated that the pretreatment absolute NLR cut-off point equal to or greater than 2.4 was a significant independent predictive biomarker of the chemotherapy-induced FN (odds ratio = 2.810, 95%,; CI 1.061 - 7.442; p = 0.038). The predictive performance of the high level of absolute NLR was an acceptable discrimination [AUC= 0.7626 (95% and CI 0.650 - 0.875)]. Furthermore, a calibration curve and the Hosmer-Lemeshow test to assess the accuracy of the predictive model showed a goodness of fit for a logistic predictive model (Hosmer-Lemeshow chi2 = 2.50; p = 0.645). Conclusions: Pretreatment absolute NLR would be a useful predictive biomarker for febrile neutropenia after the first cycle of adjuvant chemotherapy for breast cancer that would be simple and easy to integrate in daily practice without extra costs.
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Carmona-Bayonas, Alberto, Paula Jiménez-Fonseca, Juan Virizuela Echaburu, Maite Antonio, Carme Font, Mercè Biosca, Avinash Ramchandani, et al. "Prediction of Serious Complications in Patients With Seemingly Stable Febrile Neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a Prospective Cohort of Patients From the FINITE Study." Journal of Clinical Oncology 33, no. 5 (February 10, 2015): 465–71. http://dx.doi.org/10.1200/jco.2014.57.2347.
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Purpose To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. Patients and Methods We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. Results We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). Conclusion CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.
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Shirakawa, Tsuyoshi, Ken Kato, Naoki Takahashi, Hirokazu Shoji, Tetsuji Terazawa, Yoshitaka Honma, Satoru Iwasa, et al. "A retrospective comparison study of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received fluoropyrimidine and platinum-based chemotherapy." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 112. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.112.
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112 Background: Fluoropyrimidine plus platinum (FP)-based chemotherapy has been widely used as a first-line regimen for advanced or recurrent esophageal cancer (EC). Although the taxanes have shown efficacy in esophageal cancer after FP-based chemotherapy, there is no standard regimen for second-line chemotherapy (SLC). We conducted a retrospective study to investigate the clinical features of taxane therapy in SLC of EC. Methods: The selection criteria were pathologically proven EC; advanced or recurrent disease that had previously been treated with FP at our hospital; performance status 0-2; and adequate organ functions. The FP regimens used included 5-FU or S-1 and cisplatin or nedaplatin. Docetaxel (DTX) was administerd at 70mg/m2 triweekly for 6 weeks with 1 week’s rest. Paclitaxel (PTX) was administered at 100mg/m2 weekly with the same schedule. Overall survival of PTX was compared to DTX with baseline prognostic factors adjusted, using Cox proportional hazard model. Results: The analysis covered 110 patients over the period from August 2006 to June 2012. The median age was 64 years (range 39-83); 97 males and 13 females; 108 squamous cell carcinomas and 2 adenocarcinomas; 34 advanced and 76 recurrent; cStage I/II/III/IV at diagnosis 8/21/49/32; PS 0/1/2 score 20/81/9; DTX treatment 82 patients and PTX treatment 28. Progression-free survival and overall survival were 2.3 & 6.1 months with PTX and 2.8 and 6.9 months with DTX (no significant difference). The response rates were PTX/DTX/Total 11.1%/3.7%/5.5%. Hazard ratio of overall survival between DTX and PTX was 1.054 with adjusted by PS, sex and number of metastasis. The rate of grade 3-4 neutropenia was higher with DTX (28%) than with PTX (7%). Grade 3 febrile neutropenia was seen in 3.7% of DTX-treated patients but in no PTX patients. Grade 2 or more fatigue was seen in 16% of DTX patients and 10% of PTX ones, and grade 2 or more neuropathy was seen in 1.2% of DTX patients and 32% of PTX ones. Conclusions: PTX and DTX were both effective in SLC of EC, but the toxicity profiles of the two regimens differed. In terms of febrile neutropenia or fatigue, PTX seems more appropriate for SLC of EC.
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Colombo Bonadio, Renata RC, Renata Gondim Meira Velame Azevedo, Guilherme Harada, Vanessa Costa Miranda, Patricia Alves de Oliveira Ferreira, Daniela Freitas, Elias Abdo Filho, Flavia Gabrielli, Maria Del Pilar Estevez-Diz, and Samantha Cabral Severino da Costa. "Adjuvant carboplatin and paclitaxel chemotherapy followed by radiotherapy in high-risk endometrial cancer: A retrospective analysis." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e17115-e17115. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17115.
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e17115 Background: It remains unclear which is the best chemotherapy (CT) regimen and what is the role of adding radiotherapy (RT) to adjuvant CT in high-risk endometrial cancer. Methods: We performed a retrospective analysis of the patients (pts) with high-risk endometrial cancer (endometrioid histology stages III-IVA or carcinossarcoma/ clear cells/ serous histology stages I-IVA) treated with adjuvant carboplatin (AUC 5) and paclitaxel (175 mg/m2), every 3 weeks, for 6 cycles, followed by RT (conformal external beam radiotherapy to pelvic or pelvic and paraortic fields with 45Gy-54Gy plus weekly vaginal brachytherapy with 20Gy in 4 fractions). Pts were treated from 2010 to 2016 at a Brazilian public cancer center. Medical records were reviewed for demographic, clinicopathologic and outcome information. Data was analyzed for overall survival (OS), disease-free survival (DFS), prognostic factors and toxicity. The Kaplan-Meier method was used for survival analysis and Cox proportional hazard model for prognostic factors. Results: 146 consecutive pts were evaluated. Median age was 62 years (range 35-81). Most patients had ECOG 0-1 (98%), endometrioid (53%) or serous histology (26%), grade 3 tumor (57%) and FIGO stage III (77%). Median follow-up was 26.5 months. The OS rates were 85% (95% CI 75 – 91%) in 3 years and 73% (95% CI 58 – 84%) in 5 years. Factors that significantly affected OS in a multivariate analysis were FIGO stage (p = .009), pelvic lymphadenectomy (yes vs no, p = .023) and positive peritoneal cytology (yes vs no, p = .002). 3-year and 5-year DFS rates were 79% (95% CI 70 – 86%) and 68% (95% CI 52 – 80%), respectively. The initial site of recurrence was limited to the pelvis in 3% of the pts, within the abdomen in 1% and extra-abdominal in 11%. Grade 3/4 AEs occurred in 47% of the pts and were mainly hematologic toxicity (43%). There were only 3 cases of febrile neutropenia and 4 cases of hospitalization due to toxicity. Conclusions: Our data suggests that adjuvant carboplatin and paclitaxel, followed by RT, in high-risk endometrial cancer is safe and effective. Low rates of pelvic recurrence were observed, which might be explained by the addition of RT to adjuvant CT.
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Lee, Y. M. "Prognostic factors for adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review." International Journal of Evidence-Based Healthcare 10, no. 3 (September 2012): 273. http://dx.doi.org/10.1097/01258363-201209000-00108.
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García de Guadiana-Romualdo, Luis, Ignacio Español-Morales, María Dolores Albaladejo-Otón, Ana Hernando-Holgado, Enrique Jiménez-Santos, Patricia Esteban-Torrella, and Pablo Cerezuela-Fuentes. "Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department." Biochemia medica 29, no. 1 (December 24, 2018): 57–67. http://dx.doi.org/10.11613/bm.2019.010702.
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Introduction: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. Materials and methods: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. Results: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. Conclusion: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.
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Lee, Yee Mei, and Dora Lang. "Prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes in adult cancer patients: a systematic review." JBI Database of Systematic Reviews and Implementation Reports 9, Supplement (2011): 1–18. http://dx.doi.org/10.11124/01938924-201109641-00025.
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Lee, Yee Mei, and Dora Lang. "Prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes in adult cancer patients: a systematic review." JBI Library of Systematic Reviews 9, Supplement (2011): 1–18. http://dx.doi.org/10.11124/jbisrir-2011-535.
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Chao, Chun, John H. Page, Roberto Rodriguez, Su-Jau Yang, Julie Huynh, and Victoria M. Chia. "Chronic Comorbidities and Chemotherapy-Induced Febrile Neutropenia in Patients with Non-Hodgkin Lymphoma." Blood 120, no. 21 (November 16, 2012): 3671. http://dx.doi.org/10.1182/blood.v120.21.3671.3671.
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Abstract Abstract 3671 Background: Chemotherapy induced febrile neutropenia (FN) is a clinically important adverse event as it can impact patient survival by delaying or reducing chemotherapy dose administered. Clinical guidelines recommend granulocyte-colony stimulating factors (G-CSF) be used in cancer patients when febrile neutropenia (FN) risk is >20%. Although the myelotoxicity of the chemotherapy regimen is a key determinant of FN risk, it is now recognized that patient characteristics may increase this risk further. We conducted a retrospective cohort study to evaluate the association of chronic comorbidities to FN in patients with non-Hodgkin lymphoma (NHL). Methods: Incident NHL cases diagnosed between 2000–2009 who received chemotherapy within 12 months of cancer diagnosis were identified from Kaiser Permanente Southern California, a large managed care organization. Those who had prophylactic G-CSFs, dose-dense chemotherapy or bone marrow transplant were excluded. Comorbidities of interest included cardiovascular, liver, renal, metabolic and autoimmune disorders, anemia, previous cancer and HIV infection. History of comorbidity of interest were assessed in the 12 months prior to NHL diagnosis, and identified by ICD-9 codes or disease registries. FN was assessed only in the first chemotherapy cycle, and identified by absolute neutrophil count (ANC), ICD-9 codes for neutropenia and fever, or hospitalization with bacterial/fungal infection. Patients were followed from their first chemotherapy treatment to the start of the second cycle, death or day 28, whichever came first. Logistic regression was used to estimate the propensity score for each comorbidity; these propensity scores included patient characteristics and other comorbidities as covariates. Each comorbidity and propensity score were included in Cox models to determine associations between comorbidities and FN. We also evaluated models that additionally adjusted for cancer stage, baseline ANC, chemotherapy regimen, dose reduction, and radiation treatment prior to chemotherapy. Results: A total of 2,480 NHL patients who received chemotherapy were included. The mean age was 63.3 years. Fifty-five percent of the cases were male, and the majority of the cases were of white race (65.6%). Sixty percent of the cases received CHOP or R-CHOP. There were 236 (9.5%) patients that had FN in the first chemotherapy cycle. Anemia [adjusted hazard ratio adjusted (HR) =1.6, 95% CI, 1.2–2.2], HIV infection [HR=3.0, 95% CI 1.6–5.3], AIDS [HR=2.4, 95% CI 1.2–4.6], and rheumatoid diseases [HR=2.1, 95% CI 1.2–3.6] were all associated with a statistically significantly increased FN risk (Table 1). In addition, peptic ulcer disease, renal disease and connective tissue disease were also associated with risk of FN, although these associations were not statistically significant. HR estimates did not change materially after also adjusting for cancer stage, ANC, chemotherapy regimen, dose reduction and radiation therapy prior to chemotherapy in the Cox model. Conclusions: Our findings suggest that several chronic comorbidities may be associated with increased FN risk in the first chemotherapy cycle among NHL patients not already receiving prophylactic G-CSFs. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF use during chemotherapy treatment. Disclosures: Chao: Amgen,Inc: Research Funding. Page:Amgen, Inc: Employment, Shareholder Other. Rodriguez:Amgen, Inc: Research Funding. Yang:Amgen, Inc: Research Funding. Huynh:Amgen, Inc: Research Funding. Chia:Amgen, Inc: Employment, Shareholder Other.
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Voog, Eric, Jacques Bienvenu, Krzysztof Warzocha, Isabelle Moullet, Charles Dumontet, Catherine Thieblemont, Guillaume Monneret, Marie-Claude Gutowski, Bertrand Coiffier, and Gilles Salles. "Factors That Predict Chemotherapy-Induced Myelosuppression in Lymphoma Patients: Role of the Tumor Necrosis Factor Ligand-Receptor System." Journal of Clinical Oncology 18, no. 2 (January 1, 2000): 325. http://dx.doi.org/10.1200/jco.2000.18.2.325.
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PURPOSE: To analyze factors that predict the occurrence of chemotherapy-induced myelosuppression and, in particular, the role of the tumor necrosis factor (TNF) ligand-receptor system in lymphoma patients at the beginning of their treatment. PATIENTS AND METHODS: We investigated the predictive factors for myelosuppression after the first course of chemotherapy in a cohort of 101 consecutive, previously untreated lymphoma patients receiving regimens that include doxorubicin and cyclophosphamide. Plasma samples were tested at baseline by enzyme-linked immunosorbent assay for TNF and its soluble receptors. Univariate and multivariate analyses were performed with a forward regression procedure that included all of the parameters that were found to be significant in the univariate analysis. The dose of chemotherapy and the prophylactic treatment with granulocyte colony-stimulating factor were deliberately included in this model. RESULTS: Sixty-seven patients experienced World Health Organization (WHO) grade 4 neutropenia, and 37 patients experienced febrile neutropenia, which was responsible for WHO grade 2 through 4 infections in 23 patients. In multiparametric regression analysis, the occurrence of grade 4 neutropenia was associated with high doses of cyclophosphamide (odds ratio [OR], 19.8; P = .008) and high levels of soluble p75-R-TNF (OR, 8.52; P = .001). The duration of grade 4 neutropenia for more than 5 days was associated with the lack of hematopoietic growth factor administration (OR, 6.76; P = .004) and high levels of soluble p75-R-TNF (OR, 5.84; P = .0023). The occurrence of febrile neutropenia was associated with high doses of cyclophosphamide (OR, 4.7; P = .007), altered performance status (OR, 18.8; P < .0001) and high levels of soluble p75-R-TNF (OR, 3.49; P = .029). CONCLUSION: This study indicates that in addition to the dose of chemotherapy and the administration of hematopoietic growth factors, poor performance status and high p75-R-TNF levels can predict the occurrence of chemotherapy-induced myelosuppression in lymphoma patients. This model may help in selecting patients for prophylactic growth factor administration.
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Yamanaka, T., S. Matsumoto, S. Teramukai, R. Ishiwata, Y. Nagai, and M. Fukushima. "Predictive value of chemotherapy-induced neutropenia for drug efficacy in advanced gastric carcinoma: Analysis of prospective nationwide survey." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 15075. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15075.
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15075 Background: Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric cancer. Methods: Data obtained from a prospective nationwide survey of oral fluoropyrimidine S-1, performed in Japan between 1999 and 2000, were reviewed. Advanced gastric cancer patients with both adequate bone marrow function and no prior history of chemotherapy within 6 months before starting S-1 therapy were analyzed (N=1055). Chemotherapy-induced neutropenia was treated as a time-dependent covariate, and the hazard ratios [HRs] of death for experiencing neutropenia, compared with no such toxicity, were estimated using Cox regression model. Results: During treatment with S-1, a total of 293 (28%) patients had grade 1 or higher neutropenia. The adjusted HRs from a multivariate Cox model were 0.72 for patients with grade 1 neutropenia (95% confidence interval [CI] 0.54–0.95; P=0.0189), 0.63 for those with grade 2 neutropenia (95% CI 0.50–0.78; P<0.0001), and 0.71 for those with grade 3–4 neutropenia (95% CI 0.51–0.98; P=0.0388). Conclusions: The results of this study suggest that occurrence of neutropenia during chemotherapy is an independent predictor of better survival for advanced gastric cancer, while the absence of such toxicity indicates that the dosages of drugs are pharmacologically inadequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and patient survival. No significant financial relationships to disclose.
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Saramago, P., V. Andreozzi, J. M. Ferreira, and J. Félix. "Modelling the direct costs of chemotherapy-induced neutropenia treatment in Portuguese hospitals clinical practice." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 17081. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.17081.
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17081 Background: Neutropenia (N) and febrile neutropenia (FN) are common adverse effects of chemotherapy, resulting in increased risk of infections and hospitalizations. Both conditions account for substantial health resource utilization (HRU). The objective of this study was to evaluate HRU patterns for patients (PTS) experiencing N or FN in “real world” practice and to model the corresponding HRU cost profiles. Methods: Breast and lung cancer PTS receiving granulocyte colony stimulating factor (GCSF) to treat chemotherapy- induced neutropenia (absolute neutrophil count [ANC] =1500 cell/μL) were selected from 8 Portuguese hospitals. In the absence of a comprehensive database PTS having neutropenia were originally identified from hospital pharmacies GCSF prescription lists; afterwards, HRU frequency (hospitalization, clinical visits, complementary examinations, medication, transfusions) in relation to N or FN (ANC =1000 cell/μL and body temperature= 38.5°C over one hour) was reviewed retrospectively from clinical records. Treatment costs attributed to N/FN were calculated by multiplying HRU frequency by unit costs from the Portuguese Ministry of Health costs database. To account for the skewed nature of the data costs were modelled using generalized linear models with gamma distribution and log link. Results: The study included 50 PTS with breast cancer and 48 with lung cancer. Mean (SD) age was 60.0 (12.5) years and 61.2% were women. Mean (SD) ANC at first N was 724 (433) cell/μL. FN (mean (SD) ANC 440 (370) cell/μL) was developed by 16.5% of PTS. Mean (SD) total cost of N treatment was 922 (1162) € (28% hospitalization, 5% clinical visits, 3% complementary examinations, 54% medication, 10% transfusions). Controlling for PTS clinical and sociodemographic characteristics, total treatment cost were 3.2 (95%CI:1.9–5.2) times higher for PTS with FN (p<0.001) when compared to N PTS, 4.4% (95%CI: 0.1–7.7) greater for every 100 cell/μL decrease in ANC (p=0.03) and 2.5% (95%CI: 1.0–4.1) higher per additional year of age at N or FN diagnosis (p=0.002). Conclusions: Chemotherapy-induced neutropenia direct treatment costs were substantially incremented in febrile patients. [Table: see text]
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Gaur, Rachana, Rahul Bhardwaj, Sandeep Sharma, and Krishna Kumar Rathnam. "Clinical study of chemotherapy induced febrile neutropenia: talcott’s versus multinational association for supportive care in cancer risk assessment scoring systems." International Journal of Research in Medical Sciences 9, no. 1 (December 28, 2020): 236. http://dx.doi.org/10.18203/2320-6012.ijrms20205851.
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Background: Cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Febrile neutropenia (FN) is fever associated with abnormally low neutrophil count signifying an immunocompromised state secondary to malignancy or its treatment. The aim of this study was to evaluate clinical outcome of chemotherapy induced febrile neutropenia.Methods: This was a hospital based prospective, descriptive observational study. Patients of either sex, age (18-90 years), with cancer on chemotherapy, single oral temperature ≥101°Fahrenheit (38.3°C) or a temperature ≥100.4° Fahrenheit (38.0° C) for ≥ one hour with absolute neutrophil counts <500 cells/mm3 or <1000 cells/mm3 with a predicted decrease to less than 500 cells/mm3 in the next 24 hours, only with first febrile episode occurring during study period and prior or concurrent radiation therapy were included in this study.Results: Among 87 patients, 70 (80.5%) were less than 60 years and 17 (19.5%) were ≥60 years. The mean age of study patients was 44.46±15 years, (range 18 to 77 years), 31(35.6%) were male and 56 (64.4%) were female. Talcott’s and MASCC risk predicting tool versus outcome, p values for Talcott’s and MASCC were significant (<0.05).Conclusions: Neutropenic fever is a potentially life-threatening complication of cancer chemotherapy. MASCC and Talcott’s model can be used to identify low and high risk patients. MASCC risk index may have a better performance than the Talcott’s model in risk classification.
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Nijhuis, Claudi Oude, Willem A. Kamps, Simon M. G. Daenen, Jourik A. Gietema, Winette T. A. van der Graaf, Harrie J. M. Groen, Edo Vellenga, et al. "Feasibility of Withholding Antibiotics in Selected Febrile Neutropenic Cancer Patients." Journal of Clinical Oncology 23, no. 30 (October 20, 2005): 7437–44. http://dx.doi.org/10.1200/jco.2004.00.5264.
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Purpose To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model. Patients and Methods Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol. Results Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of €471 (US $572) for every potentially low-risk patient. Conclusion This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.
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Hansen, Bent-Are, Øystein Wendelbo, Øyvind Bruserud, Anette Lodvir Hemsing, Knut Anders Mosevoll, and Håkon Reikvam. "FEBRILE NEUTROPENIA IN ACUTE LEUKEMIA. EPIDEMIOLOGY, ETIOLOGY, PATHOPHYSIOLOGY AND TREATMENT." Mediterranean Journal of Hematology and Infectious Diseases 12, no. 1 (December 30, 2019): e2020009. http://dx.doi.org/10.4084/mjhid.2020.009.
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Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. Here, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.
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Duh, M., E. L. Toy, C. L. Porter, P. L. Books, F. Vekeman, V. Barghout, and A. T. Skarin. "Budget impact analysis of sargramostim use in patients with chemotherapy-induced neutropenia." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e20596-e20596. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e20596.
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e20596 Background: Myeloid growth factors are used to treat and prevent chemotherapy-induced neutropenia (CIN). Filgrastim and its long-acting version pegfilgrastim are granulocyte colony-stimulating factors (G-CSF), whereas sargramostim is a dual granulocyte- macrophage colony-stimulating factor (GM-CSF). This study analyzed the budget impact of substituting GM-CSF for G-CSF in the management of CIN from the perspective of a US health plan. Methods: A spreadsheet model was developed to compute annual and per-member-per-month (PMPM) costs associated with CSFs. Inputs included cancer prevalence, the proportion of patients receiving chemotherapy and G/GM-CSFs, incidence and cost of relevant adverse events (e.g., bone pain), and G/GM-CSF drug acquisition and administration costs. Incidence and cost of infection- and febrile neutropenia-related hospitalizations, based on recent analysis of medical insurance claims data, were also used. Cost savings (2006 USD) were assessed for utilization share switches from G-CSF to GM-CSF. Results: For a health plan with 1 million members, an estimated 976 patients received G/GM-CSF annually. Increasing baseline utilization shares for pegfilgrastim, filgrastim, and sargramostim of 70/30/0%, respectively, to alternative shares of 50/25/25% yielded substantial cost savings (see Table ), primarily related to G/GM-CSF acquisition and administration costs. Savings for patients switching from pegfilgrastim were greater than for patients switching from filgrastim. Results were sensitive to assumptions for drug cost and frequency of administration, but cost savings were observed for most scenarios. Conclusions: This study suggests that health plans can realize substantial cost savings by substituting sargramostim for filgrastim and pegfilgrastim in CIN patients. With 25% of sargramostim substitution, the cost saving could reach ≈$2 million for a health plan with 1 million members, or a saving of 16 cents per member per month. [Table: see text] [Table: see text]
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Lee, Yee Mei, Dora Lang, and Craig Lockwood. "Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis." JBI Library of Systematic Reviews 10, no. 40 (2012): 2593–657. http://dx.doi.org/10.11124/jbisrir-2012-31.
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Lee, Yee Mei, and Craig Lockwood. "Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: A systematic review and meta-analysis." International Journal of Nursing Practice 19, no. 6 (June 14, 2013): 557–76. http://dx.doi.org/10.1111/ijn.12099.
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Wong, M. D., D. Hershman, V. A. Morrison, B. Ding, and J. L. Malin. "Use of colony stimulating factors (CSF) for primary prophylaxis of chemotherapy-induced neutropenia in community oncology practices to reduce risk of febrile neutropenia (FN)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 17013. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.17013.
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17013 Background: In addition to proof of efficacy from randomized controlled trials (RCTs), health care decision makers need data on therapy effectiveness, specifically how well an intervention performs in routine practice. While the efficacy of filgrastim and pegfilgrastim in preventing FN has been established in RCTs, their effectiveness in community practice has not been studied. Methods: Data were obtained from medical records of patients treated with chemotherapy for a variety of malignancies in a random sample of 99 US community oncology practices in 2001 and 2003 (before and after FDA approval of pegfilgrastim in 2002). Patients receiving filgrastim or pegfilgrastim and, in 2003, every third patient not treated with a CSF, were consecutively sampled(n=6148). Only those receiving chemotherapy on 3–4 wk cycles were included in this analysis (n=3,744). Primary prophylaxis was defined as receipt of CSF within 3 days of the 1st cycle of chemotherapy. Multivariable logistic regression, adjusted for patient and treatment characteristics and weighted for patient sampling was used to estimate the odds of FN in patients who received primary prophylaxis versus those who were managed expectantly, i.e. patients who received CSF later during chemotherapy or not at all. Results: Of 3744 patients in the study population, 2966 (79%) received a CSF some time during their chemotherapy treatment. In 2003, approximately 18% of patients received CSF primary prophylaxis. Among patients who did not receive primary prophylaxis but received a CSF later during the treatment, 38% initiated CSF in the 1st cycle after day 3. In a multivariate model, increased risk of FN was associated with receiving myelosuppressive chemotherapy (OR 2.19; 95% CI 1.05–4.56) and having 3 or more drugs (vs. 1) in the regimen (OR 2.13; 95% CI 1.09–4.17). Adjusting for patient and treatment characteristics, the relative odds of FN in patients who received CSF primary prophylaxis was 0.70 (95% CI 0.50–0.98) compared with patients who either received CSF later or not at all. Conclusions: In this community practice setting, patients who received CSF primary prophylaxis had significantly lower odds of developing FN than patients managed expectantly. No significant financial relationships to disclose.
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Li, Yanli, Leila Family, Lie Hong Chen, John H. Page, Zandra K. Klippel, Lanfang Xu, and Chun Chao. "Value of Incorporating Newly Identified Risk Factors into Risk Prediction for Chemotherapy-Induced Febrile Neutropenia (FN)." Blood 128, no. 22 (December 2, 2016): 4797. http://dx.doi.org/10.1182/blood.v128.22.4797.4797.
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Abstract Introduction: Chemotherapy-induced FN is a clinically important adverse event that frequently requires hospitalization and can negatively impact treatment outcomes. Clinical guidelines recommend G-CSF primary prophylaxis when a patient's overall FN risk is >20%, so assessing individual FN risk is an essential step. Many newly discovered FN risk factors have been reported recently (eg, comorbidities such as diabetes, congestive heart failure,recent dermatologic conditions,and chronic obstructive pulmonary disease and procedures for cancer treatment). We sought to evaluate the added predictive value of these new risk factors beyond established FN risk factors. Methods: This study included patients diagnosed with lung, gastric, ovarian, colorectal, or female breast cancer or non-Hodgkin's lymphoma (NHL) at Kaiser Permanente Southern California (KPSC) between 2000 and 2009 and treated with chemotherapy. Patients who received prophylactic G-CSF or prophylactic antibiotics were excluded. Data were collected from KPSC's electronic medical records. The primary endpoint was FN in the first chemotherapy cycle. First, a reference model was developed based on a modified version of the FN prediction model published by Lyman et al (Cancer 2011;117:1917-27). Then a new prediction model based on the reference model plus additional newly identified FN risk factors was developed (predictors used in both models are shown in Table 1). Performance of the two models was evaluated by comparing their discriminative ability and calibration of predicted risk among the current study population. Discriminative ability was evaluated by examining the area under the receiver operator curve (AUC). Calibration of predicted risk was evaluated by comparing model-predicted risk to observed risk in the following FN risk ranges: 0-5%, 5-10%, 10-15%, and >15%. These ranges were chosen as approximately half of FN events occur in the first cycle; therefore, these ranges for FN risk in the first cycle are likely equivalent to 0-10%, 10-20%, 20-30%, and >30% risk over the chemotherapy course. Change in risk prediction at the individual patient level was also evaluated. For patients who developed FN, individual risk prediction was considered improved if the individual predicted risk drew closer to 100%; for patients who did not develop FN, individual predicted risk improved if it drew closer to 0%. Results: A total of 16,411 patients were included in the analysis (36% breast, 23% lung, 20% colorectal, 3% gastric, 6% ovarian cancer, and 12% NHL). Mean age at diagnosis was 60.5 years. Most patients were Caucasian. FN incidence in the first chemotherapy cycle was 4.0%. The odds ratios for the predictors in both models are shown in Table 1. Comparison ofFN risk predicted by both models and observed FN risk are shown in Table 2. Addingnew risk factors did not result in significant improvement in discriminative ability: AUC changed from 0.72 to 0.73. However, adding new risk factors led to a more accurate risk classification for 12% of patients (n = 1946 [425 + 569 + 282 + 64 + 382 + 132 + 92]) while it led to a less accurate risk classification for only 0.01% of patients (n = 2, Table 2). Ofthe 701patients who developed FN in the first chemotherapy cycle, adding the new risk factors increased the predicted risk for 16% ofpatients (n = 115), but decreased the predicted risk for 10% ofpatients (n = 70). Of the 15,710patients who did not develop FN, adding the new risk factors decreased the predicted risk for 5.7% ofpatients (n =973) but increased the predicted risk for 5.2% of patients (n = 811). Conclusions: Addition of the newly identified FN risk factors to the reference prediction model improved risk classification for FN in the first chemotherapy cycle. Since information on the new risk factors (including comorbidities such asdiabetes, congestive heart failure, chronic obstructive pulmonary disease, rheumatoid disease, osteoarthritis, other autoimmune diseases, peptic ulcer disease, thyroid disorder, liver disease, HIV,recent dermatologic conditions, and recent surgery)is readily available to clinicians, these factors could be incorporated into estimations of FN risk. Further refinement of the FN risk prediction model is warranted. Disclosures Li: Amgen: Employment, Equity Ownership. Family:Amgen: Research Funding. Chen:Amgen: Research Funding. Page:Amgen: Employment, Equity Ownership. Klippel:Amgen: Employment, Equity Ownership. Xu:Amgen: Research Funding. Chao:Amgen Inc.: Research Funding.
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Erdem, Dilek, Idris Yucel, Bahiddin Yilmaz, Guzin Demirag, Yasemin Kemal, and Fatih Teker. "Baseline lymphopenia as a prognostic marker for colorectal carcinoma." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14107-e14107. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14107.
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e14107 Background: Baseline lymphopenia has been proved to be a marker for poor prognosis, chemotherapy-induced toxicity and increased risk of febrile neutropenia, trombocytopenia and anemia in advanced solid neoplasms. This study aims to evaluate the effect of pretreatment lymphopenia on prognosis and hematological toxicity in colorectal cancer patients who received first line systemic chemotherapy. Methods: Lymphocyte count was evaluated in 386 pretreated colorectal cancer patients who do not have a seconder malignancy, HIV infection, bone involvement and primary G-CSF prophylaxis. Overall survival, progression free survival and disease free survival were calculated from date of diagnosis to date of relapse, progression and death. Kaplan-Meier, chi-square and Student-t test were used. Results: Mean follow-up was 30 months (range 1-180 months). Mean age was 57.4±12.5 years. Of all patients, 160 (41 %) were women. Rectum ( 26.2 %) and transvers colon (4.7 %) were the most and the least common anatomic locations, respectively. Mean lymphocyte count before treatment was 1964/µl (170-7000/µl). There were no relationship between lymphopenia and age, sex, performans status, presence of initial metastasis, adjuvant or palliative chemotherapy and hematological toxicity (p>0.05). Grade 3-4 hematological toxicity was found in 40 patients and was significantly higher in patients receiving bi- or tri-chemotherapy regimen (p:0.017). Among 208 patients with relapse or progression, 40 patients had lymphopenia (19.2 %). 1, 3 and 5-year OS were significantly lower in lymphopenic patients (p:0.033). DFS was longer in non-lymphopenic patients but this data didn’t have statistical significance (p>0.05). Conclusions: This study support that lymphocyte number prior to chemotherapy may be a simple but useful prognostic and predictive marker in untreated colorectal cancer patients. Patients with lower pretreatment lymphopenia have lower OS when compared to others (p<0.05). This study has the highest colorectal cancer population in the literature.
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Álvarez, José C., Sonia I. Cuervo, Edelberto Silva, Jorge A. Díaz, Lorena L. Jiménez, Daniel S. Parra, Julio C. Gómez, Ricardo Sánchez, and Jorge A. Cortés. "Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy." Antibiotics 10, no. 5 (April 29, 2021): 504. http://dx.doi.org/10.3390/antibiotics10050504.
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Patients with chemotherapy-induced febrile neutropenia (CIFN) may have changes in the pharmacokinetics (PK) compared to patients without malignancies or neutropenia. Those changes in antibiotic PK could lead to negative outcomes for patients if the therapy is not adequately adjusted to this. In this, open-label, non-randomized, prospective, observational, and descriptive study, a PK model of cefepime was developed for patients with hematological neoplasms and post-chemotherapy febrile neutropenia. This study was conducted at a cancer referral center, and study participants were receiving 2 g IV doses of cefepime every 8 h as 30-min infusions. Cefepime PK was well described by a two compartment model with a clearance dependent on a serum creatinine level. Using Monte Carlo simulations, it was shown that continuous infusions of 6g q24h could have a good achievement of PK/PD targets for MIC levels below the resistance cut-off point of Enterobacteriaceae. According to the simulations, it is unnecessary to increase the daily dose of cefepime (above 6 g daily) to increase the probability of target attainment (PTA). Cumulative fraction of response (CFR) using interment dosing was suboptimal for empirical therapy regimens against K. pneumoniae and P. aeruginosa, and continuous infusions could be used in this setting to maximize exposure. Patients with high serum creatinine levels were more likely to achieve predefined PK/PD targets than patients with low levels.
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Wang, Weijia, Sanjeev Balu, and Kim Campbell. "Cost-minimization analysis for biosimilar pegfilgrastim in the prophylaxis of chemotherapy induced (febrile) neutropenia and expanded access based on budget neutral basis." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 6645. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.6645.
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6645 Background: Pegfilgrastim (pegfil) injection is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Assuming biosimilarity of biosim-pegfil and pegfil in the prevention of febrile neutropenia, we estimated cost minimization of conversion from pegfil to biosim-pegfil and subsequent potential expanded access due to cost savings. Methods: A cost minimization model was conducted based on a hypothetical panel of 20,000 patients using average selling price (ASP) for one chemotherapy cycle. ASP was obtained from 1Q 2019 payment allowance limits. The simulation included two steps: 1) cost minimization was calculated per cycle (biosim-pegfil and pegfil is administered 1 dose per cycle) when patients were converted to biosim-pegfil from pegfil on ratio of 10% to 100% at 10% intervals and at a discount from 15% to 35% at 5% intervals, and 2) expanded access to biosim-pegfil was calculated based on budget neutrality. Since pegfil has two forms of availability (Neulasta and Neulasta-Onpro) with the same price, results were to either conversion scenario. Results: Per-cycle per-patient cost minimization from converting pegfil to biosim-pegfil ranged from $702.27 (15% discount) to $1,638.63 (35% discount). For 20,000 patients, this yields savings of over $14 million (15% discount) to $32 million (35% discount) at 100% conversion rate. When half the patients were converted to biosim-pegfil, savings could range from > $7 million (15% discount) to > $16 million (35% discount). With 100% conversion rate and 15% discount, 3,529 additional patients could be treated with the savings generated. At 50% conversion rate, cost savings could be applied to another 1,765 patients with 15% discount, 3,333 patients with 25% discount, and 5,385 patients with 35% discount, respectively. Conclusions: Conversion from pegfil to biosim-pegfil can lead to potential cost savings and these savings can be applied to offer increased access to supportive care with biosim-pegfil for patients receiving chemotherapy on a budget-neutral basis. For payers with larger populations, savings can be substantial. More studies are warranted to evaluate such potential cost savings due to use of biosim-pegfil over reference pegfil.
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Shirasaki, Ryosuke, Nobu Akiyama, Haruko Tashiro, Takuji Matsuo, Tadashi Yamamoto, Yoko Oka, Kazuo Kawasugi, and Naoki Shirafuji. "3D index calculated from duration and severity of neutropenia and a degree of fever as prognostic factors predicting mortality of chemotherapy-induced febrile neutropenia in hematologic malignancies." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 9053. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.9053.
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9053 Background: Risk stratification of patients with febrile neutropenia (FN) is important to select the suitable therapeutic option. Although the MASCC scoring system is used as a reliable risk-discriminator, the objective evaluation of “burden of illness” has been difficult to be pointed-out. The latest IDSA Guidelines on FN proposes a set of risk factors based on the expert’s recommendations. The present study demonstrates usefulness of newly proposed 3D-index on predicting mortality of chemotherapy-induced FN in hematologic malignancies (HM). Methods: Patients with HM admitted to our hospital between Jan 2008 and Dec 2011 were enrolled, and data from 282 FN episodes in 129 FN patients including 20 infection-associated deaths were retrospectively analyzed to determine useful prognostic factors on the mortality of FN. Correlation between mortality and 59 characteristics including 3D-index were examined by univariate analysis and receiver operating characteristic curve analysis. 3D-index is a duration and severity of neutropenia and degree of fever. Total duration of days during neutropenia was not calculate at the time of risk evaluation. 3D-indexes after three and five days from the start of FN were also analyzed. Results: 32 out of 59 characteristics were significantly correlated with mortality by univariate analysis. Among them, 3D-index and 3D-indexes after three and five days were demonstrated as more useful factors (3D-index, p=0.0015; 3D-index after three days, p=0.0030; 3D-index after five days, p=0.0044). And 3D-index after three days over 4000 indicates patients' mortality above 20%, index 2600-4000 15-20% , index 900-2600 10-15%, and index below 900 below 10%, respectively. Conclusions: 3D-indexes after three days were suggested as useful predictors for infection-related mortality during FN. It was suggested that FN patients were categorized into four risk groups according to the value.
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Sanna, Marco, Giovanni Caocci, Antonio Ledda, Elisabetta Belardinelli, Pietro Garau, Alessandro Fanni, Claudio Romani, and Giorgio La Nasa. "Identification of a Predictive Pre-Chemotherapy Score for Febrile Neutropenia - the Fnipi INDEX." Blood 136, Supplement 1 (November 5, 2020): 16–17. http://dx.doi.org/10.1182/blood-2020-134659.
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Introduction Febrile neutropenia (FN) is a leading cause of morbidity and mortality in hematology; typically, patients considered at high risk of FN are those who experience chemotherapy-induced neutropenia longer than 7 days. Other potential risk factors have been reported to impact on mortality but evidence is scarce. Also, clinicians still lack valid prediction model to identify patients at increased risk of FN. Methods We retrospectively analyzed a cohort of 100 consecutive patients who underwent intensive chemotherapy cycles (ICC) for several hematologic malignancies from October 2019 to February 2020, for a total of 368 chemotherapy courses. All patients were evaluated for age, sex, diagnosis, central line catheter, disease status, chemotherapy regimen, number of previous ICC administered, antibiotic prophylaxis, antimycotic prophylaxis, antiviral prophylaxis, anti-hepatitis B reactivation prophylaxis, G-CSF therapy, pegylated (PEG)-G-CSF therapy, previous appendectomy, diabetes, chronic obstructive pulmonary disorder (COPD), previous FN. A binary logistic regression was used to evaluate the association between independent variables and FN; statistically significant variables were included in a FN predictive score. Results In univariate analysis, an higher incidence of FN was found in patients with active disease (p<0.001, HR=3.98, 95%CI= 2.07-7,66), AML diagnosis (p<0.001, HR=6,6, 95%CI= 2.82-15.6), previous appendectomy (p<0.001, HR=3.45, 95%CI=1.65-7.2), diabetes (p<0.001, HR=4.23, 95%CI= 1.77-10.1), central line catheter in comparison with peripherally inserted central catheter (PICC) or no central line catheter (p<0.001, HR=2.66, 95%CI=1.36-5.1), CHOP like chemotherapy (p<0.001, HR=0.39, 95%CI=1.28-5.3), ICC<3, (p=0.006, HR=2,6, 95%CI=1,28-5,3). In multivariate analysis only 4 variables remained significantly associated with FN incidence: AML diagnosis (p=0.007, HR=4.28, 95%CI=1.48-12.38), active disease (p=0.002, HR=3.11, 95%CI=1.5-6.45), previous appendectomy (p=0.007, HR=3.19, 95%CI=1.36-7.47) and diabetes (p=0.01, HR=3.6, 95%CI=1.34-9.67) (Figure 1). The 4 significant variables were considered in a new score called Febrile Neutropenia Incidence Prognostic Index (FNIPI). A single point was assigned to each variable, for a maximum of 4 points. The incidence of FN was found significantly higher in cycles showing a FNIPI score of 2-4 in comparison with 0-1 (p<0.001, HR=10.1, 95%CI 4.77-21.3). Conclusions We identified several pre-treatment risk factors associated with chemotherapy-induced FN risk. Here we propose a novel score, the FNIPI, based on 4 factors (AML diagnosis, active disease, previous appendicectomy, diabetes) that discriminates patients at risk of FN after ICC. Risk assessment tools could represent a useful instrument for clinicians, to develop adequate strategies in patients at high risk of FN. To note, this observation requires larger prospective cohorts to be confirmed. Disclosures No relevant conflicts of interest to declare.
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Jeurkar, Chetan, Tiffany Pompa, Ho-man Yeung, Pamela A. Crilley, David Lane Topolsky, and Michael Styler. "Chemotherapy-induced neutropenia risk models to guide the use of myeloid stimulating factors in intermediate risk chemotherapy: A cost and practicality analysis." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10086. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10086.
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10086 Background: The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have published guidelines for use of prophylactic colony stimulating factors (CSF) for patients at risk for chemotherapy induced neutropenia (CIN). Both recommend CSF if the chemotherapy regimen has a >20% febrile neutropenia (FN) risk. If the regimen is of intermediate CIN risk, the guidelines are less definitive. In this study, we looked at lung cancer patients receiving intermediate CIN risk chemotherapy and applied two risk models developed by Hosmer et al and Bozcuk et al to see if they have adjunct value to the NCCN and ASCO guidelines to more accurately predict CIN. Methods: This was a retrospective study of 43 patients with a diagnosis of lung cancer who were treated with chemotherapy at Drexel University from 2005-2016. Risk models developed by Hosmer et al and Bozcuk et al along with the NCCN and ASCO guidelines were applied to the cohort of patients. Results: The Hosmer calculator recommended giving CSF to 26 patients, the Bozuk calculator for 22 patients, the NCCN guidelines for 25 patients and the ASCO guidelines for 38 patients. Sensitivities, specificities, and pricing information for one course of filgrastim are listed for each risk model in the Table. Conclusions: In lung cancer patients receiving intermediate CIN risk chemotherapy, the Hosmer calculator had the best combination of sensitivity, specificity, and ease of use. The Bozcuk calculator, while accurate, was more difficult to use. The NCCN guidelines missed more patients with severe CIN while the ASCO guidelines gave CSF to the greatest number of patients. The cost for using CSF would have been highest using the ASCO guidelines. Therefore, we recommend the Hosmer calculator for lung cancer patients receiving intermediate risk CIN chemotherapy as it lends to accurate but judicious use of CSF. [Table: see text]
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Kan, Motoyasu, Hiroshi Imaoka, Masafumi Ikeda, Shuichi Mitsunaga, Izumi Ohno, Yusuke Hashimoto, Mitsuhito Sasaki, et al. "Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer treated with gemcitabine and nab-paclitaxel." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 324. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.324.
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324 Background: Chemotherapy-induced neutropenia (CIN) has been reported to be associated with a longer survival in patients with various cancers. The aim of our study was to assess whether CIN could also be a prognostic factor in patients with unresectable pancreatic cancer receiving treatment with gemcitabine (GEM) and nab-paclitaxel (nab-PTX). Methods: We retrospectively analyzed the medical records of pancreatic cancer patients who had been treated with GEM and nab-PTX as first-line chemotherapy. CIN was categorized on the basis of the worst WHO grade during chemotherapy: absent/mild (≦ grade 2), or severe (≧ grade 3). The background characteristics and CIN as time-varying covariates (TVCs) were analyzed as potential prognostic factors using a Cox proportional hazards model. Results: We analyzed a total of 291 patients (absent/mild CIN: 116 patients; severe CIN: 174 patients). The median time to severe CIN was 14 days (interquartile range: 10–39 days). The median overall survival (OS) was significantly longer in the severe CIN group than in the absent/mild CIN group (19.2 vs. 11.3 months; p < 0.001) After adjustments, severe CIN was identified as an independent predictor of the OS (HR, 0.54; 95% CI, 0.38–0.77; p = 0.001). In the TVC model also, severe CIN was identified as an independent factor (HR, 0.79; 95% CI, 0.68–0.92; p = 0.002). Conclusions: Severe CIN was associated with a longer survival in patients with pancreatic cancer treated with GEM and nab-PTX.
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Nina, Lathi A., Pierre Isogai, Nicole Mittmann, Carlo DeAngelis, Matthew Cheung, Knowles Sandra, Eugenia Piliotis, Neil Shear, and Scott Walker. "Comprehensiveness of Quality of Life Instruments in Capturing Concerns Related to Chemotherapy-Induced Neutropenia." Blood 112, no. 11 (November 16, 2008): 1311. http://dx.doi.org/10.1182/blood.v112.11.1311.1311.
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Abstract Neutropenia is a serious hematologic consequence of cancer chemotherapy that can lead to further complications such as febrile neutropenia (FN). FN is potentially life threatening and often requires hospitalization. Few studies have evaluated the impact of neutropenia on quality of life (QoL). This study quantified QoL using two nonneutropenia-specific instruments, the EQ-5D questionnaire, a generic tool used to measure health-related QoL, and the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, and a neutropenia-specific instrument, the Functional Assessment of Cancer Therapy - Neutropenia (FACT-N) questionnaire. The FACT-G is a 27-item questionnaire that examines QoL in patients with cancer using four subscales. A neutropenia-specific subscale (NSS) has been developed for use with the FACT-G; this combined questionnaire is the FACT-N. Data were collected from patients, who provided informed consent, and who were admitted to Sunnybrook Health Sciences Centre, Toronto, Canada, for the treatment of chemotherapy-induced FN. Linear regression models were fitted to examine the relationship of scores from the neutropenia-specific instrument with those obtained from the other instruments. Two models were fitted using the NSS as the response variable. Predictors for the regression models were the FACT-G scores for each of the subscales (physical, emotional, social and functional wellbeing) and the five domains of the EQ-5D (mobility, self-care, usual activity, pain/discomfort and anxiety/depression) along with the visual analog scale (VAS) component of this tool. The physical and emotional wellbeing subscales of the FACT-G had a strong relationship to the NSS (p < 0.05); the social and functional well-being subscales had a much weaker relationship (p > 0.5). For the EQ-5D, the pain/discomfort domain had the strongest relationship to the NSS (p=0.18); the remaining domains, with or without the VAS, all demonstrated a weaker relationship (p > 0.5). Model fit was assessed by the adjusted R2 statistic; it was 0.54 when FACT-G subscales were used as the predictors compared to −0.04 for the EQ-5D domains indicating that the FACT-G was a better predictor of neutropenia-related concerns. Neutropenia concerns appear to be more closely related to cancer specific QoL compared to general quality of life as demonstrated by the stronger relationship of the NSS to the FACT-G than to the EQ-5D. This may be due to the comprehensiveness of the FACT-G questionnaire where a possible score anywhere from 0 to 24 or 28 can be obtained in each of the subscales, compared to three-point descriptive system for each of the domains of the EQ-5D.
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Lim, Joo Han, Hyeon Gyu Yi, Moon Hee Lee, Hoon Kim, and Chul Soo Kim. "Chemotherapy Induced Neutropenic Fever Seen at Emergency Room: A Review of 102 Cases." Blood 114, no. 22 (November 20, 2009): 4530. http://dx.doi.org/10.1182/blood.v114.22.4530.4530.
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Abstract Abstract 4530 Introduction Febrile neutropenia (FN) is a major toxicity of chemotherapy in cancer patients requiring prompt medical measures. Although the FN is a situation of oncologic emergency, the diagnosis and treatment may vary among institutions, and how fast the patients are being treated often depends on competence of House Officers at Emergency Room (ER). There has been limited data regarding the clinical outcome of patients with FN who were brought to ER. Patients and Methods We evaluated the clinical manifestations, therapeutic outcomes, and risk factors of FN in a retrospective analysis of 102 adult patients who visited ER from January 1, 2006 to March 31, 2009. FN was defined as a body temperature >38°C and a neutrophil count >0.5 × 109/L on the day of fever or the day after. Results The ECOG performance status (PS) was 0 in 15 patients, 1 in 67, and 2 in 20. The patients had a mean age of 57 years (range, 25–84). Fifty four patients were male, 52 female. Underlying diagnosis was lymphoma in 30, and soid tumors other than lymphoma in 72. The mean ANC was 436.8/mm3 (range, 0–1000); 4 patients had an ANC of <10/mm3. Twenty-three patients (22.5%) died of complications related to FN. There was no statistical difference in therapeutic outcome between tumor types, i.e. lymphoma versus non-lymphoma (p=.521), PS (p=.438), sex (p=.099), depth of neutropenia (p=.162), or time intervals from visiting ER to starting antibiotic therapy (p=.414). Age was important prognostic factor in therapeutic outcome. The median age in fatal cases was 62 years where as that of non-fatal cases was 54 (p=.016). Bacteremia was documented in 19 patients among whom 10 (53%) died. Mortality was significantly higher in patients with blood culture proven bacteria than patients whose blood culture yielded no organism (p=.013). Conclusion Cases of FN seen at ER showed substantial mortality especially in elderly patients. Given the rising age in cancer diagnosis as well as therapeutic intervention, higher mortality rate associated with chemotherapy induced FN in elderly patients needs further study seeking the way to reduce the risk of death Disclosures: No relevant conflicts of interest to declare.
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Casas, A. M., J. Rifà, J. L. González Larriba, A. Carrato, and A. López Pousa. "Risk assessment model for haematologic toxicity (HT) in patients with solid tumours (ST) during the first chemotherapy (CT) cycle." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 18516. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.18516.
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18516 Background: Bone marrow supression is the main type of CT dose-limiting toxicity. Specific studies on HT impact factors are key to help establish appropriate protocols in routine patient care. Objective: to identify significant factors among demographical and clinical variables for first-cycle CT-induced HT in patients (pts) with ST. Methods: Data was obtained from the Delfos Study, a multicentre prospective-cohort non-interventional study in Spain. To obtain a predictive model of logistic regression (LR), we followed the hierarchical principle as a way to ensure replication of results. This model was implemented for global HT, defined as compliance with at least one of the following criteria: anaemia grade (G) ≥2, thrombocytopenia G ≥2, neutropenia G ≥3, febrile neutropenia (FN, neutropenia G ≥3 and body Tª ≥38 Cº). A ROC curve was used to determine the best value for sensitivity and specificity of the model. Values were chosen so that both sensitivity and specificity resulted ≥70% and among the resulting possibilities, and due to study nature, the one providing higher specificity was taken. Results: A total of 1,194 pts with ST (breast, 37.9%; lung, 17.6%; colorectal, 15%; other, 29.5%) were included in 88 Spanish medical oncology health centres. Most pts were women (56%), mean age (SD) of 58(12) yrs. The LR model obtained predicted the global HT (pChi-sq < 0.0005), and includes the following factors: gender, tumour type, treatment intention, TNM-(T), TNM-(N), baseline haemoglobin (Hb), baseline lymphocyte count (LC), AST and the interaction gender-treatment intention. From those, five were statistically significant at the 0.05 level: baseline Hb (p < 0.0005, OR = 0.555), baseline LC (p = 0.026, OR = 0.8), type of treatment intention -neoadjuvant- (p = 0.013, OR = 0.265), TNM-(N) (p = 0.008, OR = 1.261), and interaction gender-treatment intention (p = 0.014). Inherent sensitivity and specificity of the equation were, respectively, 71.9% and 75.8%. Conclusions: A risk prediction model for global first-cycle CT-induced HT in pts with ST in Spain was implemented. Five prediction factors were identified. Baseline Hb and LC, as well as neoadjuvant intention, were inversely associated with HT. Toxicity increased with the number of affected lymph nodes. No significant financial relationships to disclose.
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Wang, Weijia, Edward Li, Kim Campbell, Ali McBride, and Steve D'Amato. "Economic Analysis on Adoption of Biosimilar Granulocyte Colony-Stimulating Factors in Patients With Nonmyeloid Cancer at Risk of Febrile Neutropenia Within the Oncology Care Model Framework." JCO Oncology Practice 17, no. 8 (August 2021): e1139-e1149. http://dx.doi.org/10.1200/op.20.00994.
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PURPOSE: Value-based programs, such as the Oncology Care Model (OCM), seek to improve care for patients undergoing chemotherapy, while reducing total costs. The purpose of this study is to quantify the impact of adopting biosimilar granulocyte colony-stimulating factors (G-CSFs) for febrile neutropenia (FN) primary prophylaxis (PP) from a US practice perspective. METHODS: A 1-year economic analysis on real-world direct drug costs and health care resource utilization was conducted in a hypothetical cohort of 500 patients with nonmyeloid cancer receiving chemotherapy. The first model simulated total cost savings of biosimilar versus reference G-CSFs over six cycles of chemotherapy. The second model evaluated cost and outcome implications of expanding the use of biosimilar G-CSFs to an additional 10% of patients at intermediate FN risk. RESULTS: Based on real-world evidence over 1 year, a total of 121 of 500 patients received G-CSF prophylaxis resulting in cost savings that ranged from $0.54M US dollars (USD) (short-acting, eg, filgrastim) to $1.68M USD (long-acting, eg, pegfilgrastim) when switching from reference to biosimilar G-CSFs. Expanding the use of biosimilar G-CSFs allowed an additional 24 patients to receive prophylaxis of FN, leading to cost savings of $0.03M USD or $1.19M USD, with a reduction of $0.08M USD in FN-related resource utilization cost. The per-patient per-year cost saving for long-acting G-CSFs was about $3,000 USD. CONCLUSION: The implementation of biosimilar versus reference G-CSFs to OCM-participating practices results in a reduction of costs and facilitates achieving OCM metrics by improving patients' outcomes while expanding biosimilar G-CSFs access to patients at intermediate risk of chemotherapy-induced FN.
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Hershenfeld, Samantha A., Kimberly Maki, Lana Rothfels, Cindy Susan Murray, Aaron D. Schimmer, and Mary Doherty. "Sharing Post-AML Consolidation Supportive Therapy with Local Centers Reduces Patient Travel Burden without Compromising Safety and Efficacy of Care." Blood 126, no. 23 (December 3, 2015): 534. http://dx.doi.org/10.1182/blood.v126.23.534.534.
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Abstract AML (acute myeloid leukemia) is frequently treated with intensive induction and consolidation chemotherapy that often requires prolonged admissions to hospital. Our group and others demonstrated that consolidation chemotherapy for AML can be safely and effectively administered to selected patients on an ambulatory basis. However, this ambulatory care is centralized in quaternary centers, requiring some patients to travel long distances to these specialized centres. Recently, we developed a shared care model where patients receive their consolidation chemotherapy for AML at the specialized quaternary care center, but receive post-consolidation supportive care including blood checks, transfusions, and treatment for febrile neutropenia at their local hospitals. Here, we reviewed the impact of our new model of care with a focus on savings in travel time and distance. Between 2009-2013, 73 patients with AML (n=61,) or APL (n=12) received post-consolidation care after CR1 at 14 local centers in the province of Ontario. These centers were regional cancer centers staffed by oncologists and/or hematologists experienced in the management of cytopenias and febrile neutropenia. However, these centers did not provide induction or consolidation chemotherapy for AML. Patients were seen at least weekly as out-patients at these hospitals while recovering from their consolidation chemotherapy. These centers were located a median of 70 km (range: 36-190) from the quaternary centre (The Princess Margaret Cancer Centre in Toronto, Canada). The 73 patients received 137 cycles of intensive consolidation where the post-consolidation care was provided by their local centre. The local centers treated a median of 2 patients (range of 1-19 patients) during the time frame evaluated. Patients receiving shared care had a median age of 57 years (range: 21.7-78.6) and 40 (54.8%) were male. 7 (9.6%) had favourable, 42 (57.5%) had intermediate, 6 (8.2%) had poor and 18 (24.7%) had indeterminate cytogenetic profiles. Google Maps (www.google.ca/maps) was used to calculate the distance travelled and estimated travel time between the patient's home and the quaternary centre or their local centre. Use of toll roads was permitted to achieve the fastest and shortest distance. Patients in the shared care model travelled a mean distance of 99.5 km ± 57.8 (median: 87.8 range: 28.4-266 km) each way to the quaternary care centre versus 26.3 km ± 33.6 (median: 14.5 range: 0.55-211 km) each way to their local treatment centre (p <0.001 for difference in means by t-test). The estimated mean time to travel from their home to the quaternary center was 71.6 ± 38 minutes (median: 62 range: 29-170) and the estimated time to travel to their local center was 23.3 ± 21.9 minutes (median: 18 range: 2-137) (p <0.001 for difference in means by t-test). Thus, by receiving post-consolidation care locally, patients saved a mean round trip travel distance of 146.5 km ± 99.6 and 96.7 min ± 63.4 of round trip travel time per visit compared to travelling to the quaternary care centre. To assess the safety and efficacy of the shared care model, we compared the survival of the patients who received shared care to that of the other 344 patients with AML (n=297) or APL (n=47) who received consolidation chemotherapy in CR1 during the same time frame and remained at the quaternary care centre for all of their post-consolidation care. Gender, age and cytogenetic risk did not significantly differ between the shared care group and the group of patients receiving all of their care at the quaternary center (p>0.05). There was no significant difference in overall survival between the 2 groups (p value of log-rank test >0.05). 30, 60, and 90 day survival from start of consolidation chemotherapy was 98.6%, 97.2%, and 95.9% for the patients receiving shared care and 98.8%, 97.1%, and 95.3% for patients receiving all of their care at the quaternary center. Multivariate Cox proportional hazards model revealed no significant increase in hazard of death for the Shared Care patients compared to control when controlling for age, gender, AML vs. APL and cytogenetic prognosis (p value >0.05). Thus, a collaborative care delivery model utilizing partnerships with regional centres for post-consolidation care in AML reduces patient travel burden while maintaining safety and efficacy. Disclosures No relevant conflicts of interest to declare.
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Banh, Cindy, Kendall Valsvik, Alejandra Arredondo, Kassie Notbohm, Abhijeet Kumar, Lee D. Cranmer, Andrew S. Kraft, Ivo Abraham, and Ali McBride. "Transitioning adriamycin ifosfamide mesna (AIM) chemotherapy in sarcoma patients to the outpatient setting: Evaluation of outpatient chemotherapy in an oncology care model setting." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19149-e19149. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19149.
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e19149 Background: The combination of doxorubicin, ifosfamide and mesna (AIM) significantly improves outcomes among patients with advanced soft tissue sarcomas. The rising cost of inpatient care, alternative payment model changes and patient preferences has prompted institutions to consider shifting therapy to the outpatient setting. However, the safety and feasibility of outpatient AIM chemotherapy is not well established. The University of Arizona Cancer Center developed an Outpatient Program (OP) to facilitate administration of traditional inpatient chemotherapy regimens in the outpatient setting. We transitioned AIM based chemotherapy to the outpatient setting based on selective criteria and caregiver support. The transition to outpatient treatment could lead to large cost-savings implications under the oncology care model. Methods: The current retrospective analysis evaluated the safety and efficacy of outpatient AIM chemotherapy for sarcoma administered in the outpatient setting. An economic study evaluated AIM in the outpatient setting, address, cost of labs, chemotherapy and bed days saved from transitioning chemotherapy from the inpatient setting. Results: Twenty-one patients with soft-tissue sarcoma were treated with outpatient AIM, for a total of 83 cycles. The median age was 60 (27-73) with 6 females and 15 males being evaluated. The median number of cycles per patient was 3.9 (range, 1-6), an average of 4.68 days of infusion days per cycle. Notable side effects included three patients ifosfamide-induced neurologic syndrome and 2 with hematuria. Acute grade 3 and 4 hematological toxicities were observed in 16 and 15 of patients, respectively with 11 occurrences of febrile neutropenia in 9 patients. Of the 21 patients, 15 patients (71%) were hospitalized at least once and 9 patients (43%) were hospitalized due to neutropenic fever. Total bed days saved by transitioning AIM outpatient was 390, for a total hospital cost savings of $1,043,250. Current costs savings for laboratory, chemotherapy and patient assistance access is still being tabulated. Conclusions: The combination of ifosfamide and mesna as a continuous outpatient infusion is feasible and well-tolerated using proper selection of patient and caregiver evaluation. This new model of administration provides an opportunity to decrease cost of care, improve patient satisfaction and reduce utilization of healthcare resource for community and academic cancer center sites.
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Bozec, Alexandre, Nicolas Fakhry, Charlotte Dupuis, Benjamin Lallemant, Marc Alfonsi, Karen Benezery, Christian Righini, et al. "Induction chemotherapy with docetaxel, cisplatin, and 5FU (TPF) in unresectable advanced head and neck squamous cell carcinoma: Retrospective analysis of 300 cases and proposal for a prognostic index." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e16055-e16055. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e16055.
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e16055 Background: Phase III studies have demonstrated that induction chemotherapy with TPF followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced unresectable head and neck squamous cell carcinoma. These studies have been done in highly selected patients. The aim of our study is to confirm these data in unselected patients and to identify prognostic factors of tolerance and survival. Methods: Between October 2005 and June 2010, 300 patients from 5 institutions with locally advanced neck and head cancer received at least one induction cycle, followed by locoregional radiotherapy (R) associated or not with platinum (P) or cetuximab (C)-based chemotherapy. Results: Mean age was 56 years old (range 31-76). Performance status was 0 or 1 in 97% of patients and 50 % of them presented current alcohol intoxication. 69% (n=208) received 3 cycles of TPF, and 91% (n=268) underwent R associated or not with P (n=167) or C (n=51). 52% of patients (n=156) received the conform treatment (ie 3TPF + RP or RC). Grade 3-4 toxicities have been reported in 19% (n= 57), including 3% febrile neutropenia (n=9) and 7% kidney failure (n=22). Grade 3-4 toxicity, during TPF induction, led systematically to permanently discontinuation of the chemotherapy. Overall response rate after TPF induction was of 88% with 23% of complete response. After a median follow-up of 21 months, median progression-free survival and cause-specific survival (SS) were not reached. Median overall survival (OS) was 49 months (95% CI 31.2-66.8). SS and OS were significantly improved (p<0.0001) in patients who received the conform treatment. In multivariate analysis the probability of death related to cancer or to toxicities induced by treatment was increased for hemoglobin level ≤ 12.6g/dl or GGT level ≥ 77U/I [HR = 3.45 (95% CI: 1.50-7.93) p=0.0029]. Conclusions: We propose to use a biological index based on baseline hemoglobin and GGT levels to select patient for induction therapy in SCCHN. This simple index, predictive of treatment conformity and specific survival, needs further prospectives investigations.
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Li, Edward C., Dylan Mezzio, Kimberley J. Campbell, Andrew Spargo, and Gary H. Lyman. "Cost-effectiveness of filgrastim-sndz as primary prophylaxis (PP) versus secondary prophylaxis (SP) to prevent chemotherapy-induced febrile neutropenia (FN) in breast cancer patients at intermediate risk." Journal of Clinical Oncology 38, no. 29_suppl (October 10, 2020): 73. http://dx.doi.org/10.1200/jco.2020.38.29_suppl.73.
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73 Background: According to clinical practice guidelines, the threshold for routine myeloid growth factor (MGF) PP is a high risk (>20%) of developing FN. However, in response to the COVID-19 pandemic, a recent recommendation expands this threshold for using MGF PP to include patients at intermediate risk (10-20%) of developing FN, with the goal of reducing emergency room and hospital visits. Patients with breast cancer receiving potentially curative chemotherapy consisting of docetaxel or paclitaxel (every 21 days) are at an intermediate risk (10-20%) of developing FN. This study evaluates the cost-effectiveness of PP vs. SP using a biosimilar MGF, filgrastim-sndz, in early-stage breast cancer patients at intermediate risk of FN. Methods: A Markov model with a lifetime horizon was constructed to evaluate the total costs and clinical outcomes when using filgrastim-sndz as PP vs. SP in 56 year old early-stage breast cancer patients receiving adjuvant docetaxel (following doxorubicin/cyclophosphamide) every 3 weeks for 4 cycles. Patients had ≥1 FN risk factor (i.e., recent surgery) without the receipt of anti-HER2 therapy, representing a 16% baseline FN risk. Average Sales Price (ASP) calculated from the Centers for Medicare & Medicaid Services July 2020 ASP Drug Pricing File was used as the filgrastim-sndz cost. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a United States payer perspective. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results: Filgrastim-sndz as PP vs. SP provided an additional 0.102 FN events avoided, 0.065 LYS, and 0.056 QALYs at an incremental cost of $2,106. The ICERs were $20,656, $32,624 and $37,333 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. In the PSA, the likelihood of cost-effectiveness at a willingness-to-pay (WTP) threshold of $50,000 per QALY gained was 71.3%. Conclusions: For early-stage breast cancer patients at intermediate risk of FN receiving adjuvant docetaxel with 1 or more risk factors, PP with filgrastim-sndz compared to SP is cost-effective based on a WTP threshold of $50,000/QALY. [Table: see text]
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O'Halloran, Katrina, Sheetal Phadnis, Laura Metrock, Gregory Friedman, Tom Davidson, Nathan Robison, Girish Dhall, and Ashley Margol. "MEDB-86. A re-induction regimen for children with recurrent medulloblastoma." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i126—i127. http://dx.doi.org/10.1093/neuonc/noac079.460.
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Abstract Medulloblastoma is the most common malignant brain tumor of childhood. Despite multi-modal therapies, ~30% of patients experience disease recurrence, which portends a poor prognosis. At initial recurrence, intensive chemotherapy may be effective prior to various consolidation therapies including high dose chemotherapy with autologous stem cell rescue or irradiation. We report outcomes for nine children treated at two institutions with the following regimen: cyclophosphamide 1500mg/m2/dose days 1,2; irinotecan 125mg/m2/dose days 1,8; temozolomide 150mg/m2/dose days 1-5, and oral etoposide 50mg/m2/dose days 1-7. Patients received 2-4 cycles based upon disease response and physician preference. The mean time from initial diagnosis to first recurrence was 19 months. After receiving two cycles of therapy, two patients had complete response (CR) and proceeded to consolidation. Of the remaining seven patients, five had partial response (PR) and two had stable disease (SD). Overall response rate was 78% after 2 cycles. Two patients with PR proceeded directly to consolidation with irradiation. Five patients (3 PR, 2 SD) received 2 additional cycles. After four cycles there was one CR, two with minimal residual disease, one SD and one progressive disease (PD). Four patients (44%) are alive with no evidence of disease (NED). One patient died of consolidation-related toxicity but had NED at time of death 28 months from initial recurrence. Five patients developed PD. Two patients died of disease, two are alive with disease, and one is alive with NED after PD and additional therapy. There were no treatment-related deaths. Infection was the most common complication. Five patients had febrile neutropenia and two developed sepsis. One patient required dose reduction for prolonged thrombocytopenia. Peripheral blood stem cell collection was achieved in all patients for whom it was attempted. This re-induction regimen is generally well-tolerated and effective in inducing responses for children with recurrent medulloblastoma.
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Li, Edward C., Dylan Mezzio, Andrew Spargo, Kimberley J. Campbell, and Gary H. Lyman. "Cost-effectiveness of filgrastim-sndz as primary prophylaxis (PP) versus secondary prophylaxis (SP) to prevent chemotherapy-induced febrile neutropenia (FN) in non-small cell lung cancer (NSCLC) patients at intermediate risk." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19401-e19401. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19401.
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e19401 Background: Patients with nonmetastatic NSCLC receiving platinum-based chemotherapy are at an intermediate risk (10-20%) of developing FN; clinical practice guidelines recommend assessing whether these patients have FN risk factors before considering myeloid growth factor (MGF) prophylaxis. Most NSCLC patients receiving chemotherapy have ≥1 FN risk factors, and while PP leads to lower rates of FN across all cycles, it is more costly compared to SP. This study evaluates the cost-effectiveness of PP vs. SP using a biosimilar MGF, filgrastim-sndz, in NSCLC patients at intermediate risk of FN. Methods: A Markov model with a lifetime horizon was constructed to evaluate the total costs and clinical outcomes of using filgrastim-sndz as PP vs. SP in NSCLC patients 61 years old receiving adjuvant carboplatin/paclitaxel every 3 weeks for 4 cycles. Separate analyses were conducted for patients with 0 FN risk factors (0RF) and with ≥1 FN risk factors (1+RF), representing 11.3% and 18% baseline FN risk, respectively. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a United States payer perspective. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results: For patients with 0RF, use of filgrastim-sndz as PP vs. SP provided an additional 0.056 QALYs (0.079 LYS) at an incremental cost of $3,266. The ICERs were $46,815, $41,555, and $58,531 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. For patients with 1+RF, PP vs. SP added 0.090 QALYs (0.127 LYS) at an incremental cost of $1,605. The ICERs were $13,970, $12,644, and $17,805 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. In the PSA, the likelihood of cost-effectiveness at a willingness-to-pay (WTP) threshold of $50,000 per QALY gained was 31.7% for patients with 0RF and 96.6% for 1+RF. Conclusions: For NSCLC patients at intermediate risk of FN receiving adjuvant carboplatin/paclitaxel with 1+RF, PP with filgrastim-sndz compared to SP is cost-effective based on a WTP threshold of $50,000/QALY. [Table: see text]
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Mahipal, Amit, Gregory M. Springett, Nancy Burke, Barbara Bertels, Georgine Wapinsky, Khaldoun Almhanna, and Richard D. Kim. "Phase I trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 467. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.467.
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467 Background: Despite recent advances, patients with metastatic pancreatic cancer have a very poor prognosis with a median survival of less than 1 year. Sex steroid hormones may play an important role in the growth and progression of pancreatic cancer. Anti-androgen drugs have demonstrated to have activity in pre-clinical pancreatic cancer models. In this Phase 1a/Ib trial, we evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel. Methods: Pts with histologically confirmed metastatic pancreatic adenocarcinoma were included in this trial as a first-line treatment. Standard 3+3 dose escalation design was used to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg daily. Gemcitabine 1,000 mg/m2 was administered IV on days 1, 8 and 15 of 28-day cycle. The dose of nab-paclitaxel was 125 mg/m2 IV on days 1, 8 and 15. The DLT period was 28-days or until the beginning of the second cycle. Imaging studies were performed every 2 cycles. Results: Eight pts with stage IV pancreatic cancer have been enrolled in this trial, 5 pts at the first dose level and 3 pts at the second dose level. The median age was 64 years (50-80 years). All pts were male with an ECOG performance status of 1. Five pts had liver metastases. One patient was non-evaluable for DLT. No DLTs have been observed. Grade 3 treatment related AEs include febrile neutropenia (n=1), Neutropenia (n=1), ALT elevation (n=1). Grade 2 anemia and thrombocytopenia was seen in one patient. Grade 1 AEs included anemia (n=2), neutropenia (n=4), thrombocytopenia (n=3), diarrhea (n=1), fatigue (n=2), pruritis (n=1), nausea (n=1), hyponatremia (n=1) and AST elevation (n=1). Three pts had restaging studies performed and all had stable disease by RECIST criteria. There were decreases in size of target lesions in all the 3 patients along with a decrease in CA 19-9 levels. Conclusions: Enzalutamide at the dose of 160 mg daily is safe to administer in combination with gemcitabine and nab-paclitaxel. No unexpected toxicity has been observed. Cytopenias secondary to chemotherapy is common. Preliminary signals of efficacy were observed with this combination. Clinical trial information: NCT02138383.
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Lyman, Gary H., Dylan Mezzio, Edward C. Li, Kim Campbell, and Sanjeev Balu. "A cost-effectiveness analysis of primary prophylaxis (PP) versus secondary prophylaxis (SP) with biosimilar myeloid growth factors (MGFs) for preventing chemotherapy-induced febrile neutropenia (FN) in non-Hodgkin lymphoma (NHL) patients at intermediate risk." Journal of Clinical Oncology 37, no. 27_suppl (September 20, 2019): 107. http://dx.doi.org/10.1200/jco.2019.37.27_suppl.107.
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107 Background: Historically, PP with a MGF was recommended in patients with a ≥40% risk for developing chemotherapy-induced FN, based on clinical and regimen-related factors. Previous economic studies provided evidence to lower the threshold to 20%, the current high-risk threshold listed by practice guidelines. Biosimilar MGFs, such as filgrastim-sndz or LA-EP2006 (a proposed pegfilgrastim biosimilar), offer an opportunity to evaluate whether it is cost-effective to further lower the threshold for intermediate-risk regimens (i.e., 10-20% FN risk). Methods: A Markov model was constructed to evaluate the total costs and clinical outcomes of biosimilar or reference MGFs when used as PP vs. SP in patients 55 years old with NHL receiving 6 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with no additional FN risk factors. Model inputs, including MGF efficacy and acquisition costs, were estimated from publically available data and literature, as were FN hospitalization costs and clinical utilities. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a payer perspective within the United States. Deterministic and probabilistic sensitivity analyses were conducted. Results: Use of filgrastim-sndz as PP vs. SP provided an additional 0.130 QALYs (0.144 LYS) at an incremental cost of $5,999. The ICERs were $50,676, $41,761, and $46,207 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. Using LA-EP2006 as PP vs. SP provided an additional 0.166 QALYs (0.184 LYS) at an incremental cost of $17,648. The ICERs were $123,840, $95,963, and $106,265 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. Conclusions: Within NHL patients receiving R-CHOP at an intermediate risk for FN, PP with filgrastim-sndz and LA-EP2006 are cost-effective compared to their respective use as SP based on a cost-effectiveness threshold of $150,000/QALY.
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Jimenez Gordo, Ana M., Gonzalo Colmenarejo, Javier Baena Espinar, Carlos Aguado, Xabier Mielgo, Ana Pertejo, Rosa Maria Alvarez Alvarez, et al. "A multicenter analysis of the outcome of cancer patients with neutropenia and COVID-19 infection optionally treated with granulocyte colony-stimulating factor (G-CSF)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 12105. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.12105.
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12105 Background: Infection by SARS-CoV-2 can turn into an acute respiratory infection. Approximately 15% of patients will develop a distress syndrome responsible in most cases of mortality. A host hyperinflammatory response induced by a cytokine storm, is the main cause of this severe complication. Chemotherapy myelosuppression is associated with higher risk of infections and mortality in cancer patients. There have been no previous reports about the clinical management of patients with neutropenia and concomitant COVID-19. Herein, we present a multicenter experience in several hospitals during COVID-19 outbreak in neutropenic cancer patients infected by SARS-Cov-2. Methods: Retrospective clinical data were collected from clinical reports. Protocol was approved by a Clinical Research Ethics Committee (HULP: PI-4194). Inclusion criteria were cancer patients with neutropenia (<1500 cells/mm3) and concomitant COVID-19 infection. Comorbidities, tumor type and stage, treatment, neutropenia severity, filgrastim (G-CSF), COVID-19 parameters and mortality were analyzed. Exploratory analysis included a description of all data collected and bivariate analyses among different pairs of variables, including their impact in mortality in this cohort. In addition, multivariable logistic regression was used to predict respiratory failure and death as a function of multiple variables. Results: Among 943 patients with cancer screened in 14 hospitals in Spain, eighty-three patients (8%) had a febrile neutropenia and COVID-19 infection. Lung (26%), breast (22%), colorectal (13%) and digestive non-colorectal (17%) cancers were the main locations and most patients had advanced disease (67%). Fifty-three (63%) of patients included died because respiratory failure. Neumonia was presented in 76% of patients, bilateral in 47% and 12% of all patients had thrombotic events. The median of neutrophils was 650cls/mm3 and 49% received G-CSF with a median of days on treatment around 4,5 days. Among all variables related with mortality in neutropenic cancer patients with COVID-19 infection, we found that the number of days with G-CSF showed a significant trend toward worse outcome and higher mortality. In particular, a logistic regression model was developed to predict respiratory failure, as a function of the number of days of G-CSF treatment. As adjusting covariates, sex, age, treatment purpose (palliative vs curative, to adjust for patient status), tumor type, and the lowest level of neutrophils in the patient (to adjust for neutropenic status) were used. A significant effect was obtained for the days of G-CSF treatment (OR = 1.4, 95% CI [1.03, 1.92], p-value = 0.01). Conclusions: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with COVID-19, with a higher probability of worse outcome.
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McBride, Ali, Karen MacDonald, and Ivo Abraham. "Simulation modeling of budget-neutral expanded access to antineoplastic therapy from cost-savings derived from conversion to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) in early-stage breast cancer." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19371-e19371. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19371.
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e19371 Background: Biosimilars not only have the potential to reduce the cost of prophylaxis of CIN/FN but such savings could be reallocated to provide access to anti-neoplastic treatment. To demonstrate this, we simulated in a 20,000-patient panel: 1) the savings that could be realized from CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim with or without on-body injector (PEG/PEG-OBI), 2) a model of expanded access to adjuvant chemotherapy with doxorubicin/cyclophosphamide for localized breast cancer from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) the number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of doxorubicin/cyclophosphamide chemotherapy. Methods: Simulation modeling from the US payer perspective utilizing:average selling price (ASP) derived from CMS Q1 2020 reimbursement limits for PEG/PEG-OBI, pegfilgrastim-cbqv, doxorubicin and cyclophosphamide;between one and six cycles of prophylaxis in a panel of 20,000 cancer patients at risk for CIN/FN; and conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100%. Results: Using current ASP, cost-savings of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI in a panel of 20,000 breast cancer patients range from $445,163 (for one cycle of prophylaxis at 10% conversion) to $26,709,788 (6 cycles at 100% conversion). In a single cycle of chemotherapy, these savings translate into expanded access to doxorubicin/cyclophosphamide ranging from 1,286 cycles at 10% conversion from PEG/PEG-OBI to 12,861 cycles at 100% conversion. The savings over six cycles could provide between 7,717 additional cycles of doxorubicin/cyclophosphamide (at 10% conversion) to 77,166 cycles (at 100% conversion). The NNC from PEG/PEG-OBI to purchase one additional cycle of doxorubicin/cyclophosphamide is 2. Conclusions: These models demonstrate that CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv can generate significant cost savings for supportive cancer care. Further, these savings could be reallocated to provide access to curative anti-neoplastic treatment on a budget-neutral basis, thus enhancing the value of cancer care to both payers and patients.
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Antonuzzo, Andrea, Enrico Vasile, Maurizio Lucchesi, Laura Ginocchi, Luca Galli, Isa Maura Brunetti, Sergio Ricci, and Alfredo Falcone. "A new model of early supportive care and symptoms management: The experience of Pisa medical oncology." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e20711-e20711. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e20711.
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e20711 Background: Recent advances in medical oncology research and new possibilities of care create a growing number of treatment-related complications. Due to these clinical relevant toxicities a significative number of patients have to admit to our hospital emergency rooms in the recent years. Data from different institutions in Italy suggest that an integrated model of supportive care dedicated to symptoms management and not only, is more effective for cancer patient’s care. Methods: In the last seven months of 2012 we started the “supportive care-team” activity giving a dedicated-room inside the day hospital offering to the patients a direct and early management of chemotherapy toxicities (mucositis, febrile neutropenia, etc.) and “new drugs” induced toxicities (cutaneous, hypertension/cardiovascular, infective, etc.). The medical and nurse team does receive the patient without appointment, based on the severity of clinical problems and give a mobile phone consult all days in the morning. Patients receive symptomatic therapy, i.v. fluid infusions, collecting of blood samples, corrections of medical therapies (e.g. pain therapy), venous accesses management for one-day or more until resolution and physicians are able to organize further specialists evaluations. Moreover, there are strictly linked specialists such as anesthesiology involved in all cases of severe drugs adverse reactions. Other two ancillary support activities the for patients are offered by the psychologist and chaplain daily inside the day hospital. Results: During all 2012 we have delivered 13.365 courses of anticancer therapies in 1,358 patients. All these were outpatients. During the last 7 months of 2012 we have made 761 unplanned visits (median number/day 6, range 0-13) and the team did respond to 1,138 phone calls (median number/day 9, range 2-24). Conclusions: These analysis does attempt to answer to the main question of reducing hospitalizations and their related costs. Our new organizative model prompt to maintain much more the management of oncologic patients inside the oncologic department and to increase the feasibility of patient’s continuos care, improving symptoms control and patient’s quality of life.
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McBride, Ali, Karen MacDonald, and Ivo Abraham. "Cost efficiency and budget-neutral expanded access to antineoplastic therapy from cost-savings derived from conversion to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN):Simulation modeling in metastatic pancreatic cancer." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 441. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.441.
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441 Background: Biosimilars have contributed to the reduction in the cost of prophylaxis of CIN/FN in recent years. Savings generated from conversion to biosimilars could be reallocated on a budget-neutral basis to provide expanded access to additional prophylaxis or to anti-neoplastic treatment. To demonstrate this, we simulated: 1) the savings that could be realized from CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv (BIOSIM-PEG) over reference pegfilgrastim with or without on-body injector (PEG/PEG-OBI), 2) a model of expanded access to BIOSIM-PEG from cost-savings achieved from conversion from PEG/PEG-OBI, 3) a model of expanded access to chemotherapy with oxaliplatin, leucovorin, irinotecan, and fluorouracil (FOLFIRINOX) for metastatic pancreatic cancer (mPC), 4) the number-needed-to-convert (NNC) to BIOSIM-PEG to purchase one additional treatment of BIOSIM-PEG, and 5) the NNC to purchase one cycle of FOLFIRINOX. Methods: This simulation modeling from the US payer perspective utilized: 1) a blended rate of average selling price (ASP; derived from CMS Q4 2020 reimbursement) and wholesale acquisition cost (WAC; Redbook) for PEG/PEG-OBI, BIOSIM-PEG, and all FOLFIRINOX agents proportionate to the estimated 2020 incident pancreatic cancer age distribution per Surveillance, Epidemiology, and End Results Program (67.6% Medicare-insured patients ≥65 years of age; 32.4% commercially insured patients <65 years); 2) between one and twelve cycles of prophylaxis in a panel of 2,500 mPC patients treated with FOLFIRINOX; and 3) conversion rates from PEG/PEG-OBI to BIOSIM-PEG ranging from 10%—100%. Results: Using a current blended ASP/WAC rate, cost-savings of BIOSIM-PEG over PEG/PEG-OBI in a panel of 2,500 mPC patients range from $188,780 (for 1 cycle of prophylaxis at 10% conversion) to $22,653,609 (12 cycles at 100%). In a single cycle of chemotherapy, these savings translate into expanded access to additional BIOSIM-PEG prophylaxis ranging from 53 cycles at 10% conversion from PEG/PEG-OBI to 528 cycles at 100% or to between 321 to 3,214 cycles of FOLFIRINOX, respectively. The savings over twelve cycles could provide up to 6,330 additional cycles of BIOSIM-PEG or 38,571 cycles of FOLFIRINOX (at 100% conversion). The NNC from PEG/PEG-OBI to purchase one additional cycle of BIOSIM-PEG is 4.74; the NNC to purchase once cycle of FOLFIRINOX is 0.78. Conclusions: These simulated models demonstrate the magnitude of the cost savings for CIN/FN prophylaxis that can be generated by conversion to biosimilar pegfilgrastim-cbqv. Further, these savings could be reallocated to provide access to anti-neoplastic treatment on a budget-neutral basis, thus enhancing the value of cancer care to both payers and patients.
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Chien, Amy Jo, Amelia S. Gliwa, Siti Rahmaputri, Heidi F. Dittrich, Melanie Catherine Majure, Hope S. Rugo, Michelle E. Melisko, et al. "A phase Ib trial of the cyclin-dependent kinase inhibitor dinaciclib (dina) in combination with pembrolizumab (P) in patients with advanced triple-negative breast cancer (TNBC) and response correlation with MYC-overexpression." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 1076. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.1076.
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1076 Background: Increased expression of the MYC transcriptional oncogene is found in about 70% of TNBC and is associated with poor prognosis. In MYC-overexpressing TN xenografts, CDK1 inhibition with dina results in synthetic lethality, and attenuates distant metastasis. In syngeneic models, the combination of dina with anti-PD1 therapy is synergistic and increases immune cell tumor infiltration and activation. Methods: Patients (pts) with advanced TNBC received dina IV day 1 and 8 in combination with fixed dose P 200 mg once every 21 days. Dina was dose escalated using a toxicity probability interval design targeting a dose limiting toxicity (DLT) rate of 25%. Evaluable disease and pre-treatment metastatic biopsies were required. After 17 pts were enrolled, eligibility was amended to require ≤2 lines of prior chemotherapy, and LDH ≤1.5x normal. MYC IHC was performed on baseline tumor biopsies and correlated with clinical response using Welch’s unequal variances t-test. Results: 32 pts were enrolled (median age 53, median 2 prior lines of therapy, 13 pts (41%) had disease which was previously ER+). 18 pts were enrolled in the dose escalation phase with no observed DLTs; 33 mg/m2 was determined to be the recommended phase 2 dose (RP2D). 14 additional patients were enrolled in dose expansion at 33 mg/m2, completing trial accrual. Grade ≥3 adverse events (AEs) in all pts included neutropenia (ntp) (37.5%), febrile ntp (12.5%), fatigue (12.5%), transaminitis (3.2%), and neuromuscular weakness (3.2%). Most common all grade AEs included fatigue (63%), diarrhea (63%), nausea (63%), and ntp (53%). Possible immune-related AEs included sinusitis (4 pts), hemolytic anemia (1 pt), pneumonitis (1 pt), rash (2 pts), neuromuscular weakness (1 pt), and transaminitis (1 pt). Of the 29 patients evaluable for response, 1 pt (3.4%) had a CR, 4 pts (13.8%) had a PR, and 6 pts (20.6%) had SD. MYC IHC staining on baseline metastatic tumor biopsies in 19 pts correlated significantly with clinical response. Additional biomarker testing will be reported. Conclusions: The RP2D of dina given in combination with standard dose P is 33 mg/m2 on D1, 8 of a 21-day cycle. Toxicities were generally manageable and non-overlapping. In exploratory analysis, greater MYC IHC staining correlated significantly with response to study therapy. Clinical trial information: NCT01676753 .
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Chien, Amy Jo, Siti Rahmaputri, Heidi F. Dittrich, Melanie Catherine Majure, Hope S. Rugo, Michelle E. Melisko, and Andrei Goga. "A phase Ib trial of the cyclin-dependent kinase inhibitor dinaciclib (dina) in combination with pembrolizumab (P) in patients with advanced triple-negative breast cancer (TNBC)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 1072. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.1072.
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1072 Background: Increased expression of the MYC transcriptional oncogene is found in 70% of TNBC and is associated with poor prognosis. In MYC-overexpressing TN xenografts, CDK1 inhibition with dina results in synthetic lethality, and attenuates distant metastasis. In syngeneic models, the combination of dina with anti-PD1 therapy is synergistic and increases immune cell tumor infiltration and activation. Methods: Patients (pts) with advanced TNBC were enrolled. Pts received intravenous dina day 1 and 8 in combination with fixed dose P 200 mg once every 21 days. Dina was dose escalated using a toxicity probability interval design targeting a dose limiting toxicity (DLT) rate of 25%. Evaluable disease and pre-treatment metastatic biopsies were required. After 17 pts were enrolled, eligibility was amended to require ≤2 lines of prior chemotherapy, and LDH ≤1.5x normal. Results: 22 pts were enrolled (median age 50, median 2 prior lines of therapy, 10 pts (45%) had disease which was previously ER+). Dina was dose escalated from 12 to 33 mg/m2 in 4 cohorts. No DLTs were observed. Of the first 5 patients in the 33 mg/m2 cohort, 2 pts required a dose reduction (1 pt due to recurrent grade (G) 3 fever and G2 chills; 1 pt due to recurrent G2 diarrhea, chills, fatigue), and 1 pt discontinued due to G3 hemolytic anemia. 4 additional pts were treated at 33 mg/m2 without DLT or dose reduction. G ≥3 adverse events (AEs) in all pts included neutropenia (ntp) (36.3%), febrile ntp (13.6%), and fatigue (13.6%). Most common all-grade AEs included fatigue (73%), diarrhea (59%), nausea (50%), ntp (45%), mucositis (32%), anorexia (23%). Immune-related AEs included sinusitis (3 pts), hemolytic anemia (1 pt), pneumonitis (1pt), and rash (2 pts). Of 21 pts evaluable for response, 1 pt had complete response (4.8%), 2 pts had partial response (9.5%), and 5 pts had stable disease (23.8%). Dose expansion and correlative biomarker studies are ongoing. Conclusions: The recommended phase 2 dose of dinaciclib given in combination with pembrolizumab is 33 mg/m2 on D1, 8 of 21-day cycle. Toxicities are generally manageable with dose reduction and dose delay. Clinical trial information: NCT01676753.
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Blackwell, Kimberly, Vladimir Semiglazov, Pedro Gascon, Roumen Nakov, Stefan Kramer, Arnd Schwebig, and Nadia Harbeck. "A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study)." Blood 124, no. 21 (December 6, 2014): 5133. http://dx.doi.org/10.1182/blood.v124.21.5133.5133.
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Abstract Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and hematopoietic stem cell mobilization. Filgrastim biosimilars are presently being developed for the U.S. market. Study design: A randomized, double-blind, four-group, multi-center phase III non-inferiority trial was performed with breast cancer patients treated with myleosuppressive chemotherapy. The two filgrastim products – proposed biosimilar, EP2006 (“biosimilar”) vs. originator (U.S.-licensed Neupogen®) - were compared regarding efficacy and safety. Patients included: women ≥18 years with histologically-proven breast cancer eligible for neoadjuvant or adjuvant treatment with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC regimen) given for 6 cycles. Other key inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤2 and adequate bone marrow function. Eligible patients were randomized to 4 groups with 2 of these groups alternating between the biosimilar and the originator filgrastim at the end of each cycle: 1) EP: treatment with EP2006 in all cycles; 2) EPNEU: EP2006 in Cycle 1, alternating between Neupogen and EP2006 in the following cycles; 3) NEUEP: Neupogen in Cycle 1, alternating between EP2006 and Neupogen in the following cycles; 4) NEU: treatment with Neupogen in all cycles. Patients received either biosimilar or originator filgrastim subcutaneously (daily dose of 5 µg/kg body weight) starting on Day 2 of each chemotherapy cycle until the absolute neutrophil count (ANC) recovered to 10×109/L after nadir or up to 14 days. Total duration of the study was 25 weeks: 3 weeks screening, 18 weeks treatment (total 6 cycles, 3 weeks each) and a follow-up visit 4 weeks after the last study drug administration. Primary objective was to assess the efficacy of the biosimilar compared to the originator with respect to mean duration of severe neutropenia (DSN) following Cycle 1 chemotherapy. A one-sided 97.5% confidence interval (CI) for the difference in the mean DSN calculated using ANCOVA model with factors “treatment” and “kind of therapy” and covariates “baseline ANC” was to be considered non-inferior if lower limit of this CI lies entirely above non-inferiority margin of -1 day. All secondary efficacy endpoints and safety endpoints were analyzed descriptively by treatment group. The study was conducted between December 2011 and June 2013. Results: Enrolled were 258 patients in 27 centers, of which 218 patients were randomized to treatment. The baseline characteristics were balanced between different groups. The per-protocol set included 204 patients out of 218 randomized patients. The safety set included 214 patients who received at least one dose of study drug. On average each patient received treatment for 8-9 days per cycle. The mean DSN in Cycle 1 was 1.17±1.11 days (biosimilar) and 1.20±1.02 days (originator); the mean difference in DSN was 0.04 days (97.5% CI, lower limit -0.26 days). The pre-defined non-inferiority criteria were met and the biosimilar was considered non-inferior to the originator filgrastim. The incidence of febrile neutropenia over all 6 cycles chemotherapy was comparably low in all treatment groups (EP: 2/40, 5.0%, EPNEU: 5/45, 11.1%, NEUEP: 1/44, 2.3%, NEU: 0/46, 0.0%). There was no obvious difference in incidences of treatment emergent adverse events between the treatment arms. Twelve patients experienced serious adverse events (EP: 5/53, 9.4% patients; EPNEU: 4/54, 7.4%; NEUEP: 1/55, 1.8%; NEU: 2/52, 3.8%). None of them were study drug related, including one death (in the EP treatment group due to pulmonary embolism). No subjects developed anti-drug antibodies. Conclusion: This large clinical study showed that efficacy and safety of the biosimilar was comparable to the originator filgrastim in prevention of neutropenia in patients with breast cancer. Repeated switching between the biosimilar and the originator filgrastim did not impact efficacy, safety or immunogenicity. Acknowledgment: The authors acknowledge the other investigators of the PIONEER study and acknowledge Gabor Stiegler, Sandoz Biopharmaceuticals for the medical writing. Disclosures Blackwell: Sandoz Biopharmaceuticals: Consultancy. Semiglazov:Sandoz Biopharmaceuticals: Consultancy. Gascon:Sandoz Biopharmaceuticals: Consultancy. Nakov:Sandoz Biopharmaceuticals: Employment. Kramer:Sandoz Biopharmaceuticals: Employment. Schwebig:Sandoz Biopharmaceuticals: Employment. Harbeck:Sandoz Biopharmaceuticals: Consultancy.
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Schlenk, Richard F., Jürgen Krauter, Markus Schaich, Didier Bouscary, Hervé Dombret, Ivo J. Winiger, Margaret Squier, Anita Zahlten, Lu Wang, and Oliver G. Ottmann. "Determination of the Maximum Tolerated Dose of Panobinostat in Combination with Cytarabine and Mitoxantrone As Salvage Therapy for Relapsed/Refractory Acute Myeloid Leukemia." Blood 118, no. 21 (November 18, 2011): 423. http://dx.doi.org/10.1182/blood.v118.21.423.423.
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Abstract Abstract 423 BACKGROUND: Relapsed/refractory acute myeloid leukemia (AML) is characterized by poor prognosis, with low complete remission (CR) rates after salvage therapy and low overall survival. A major challenge is to improve the CR rate, thereby increasing allogeneic hematopoietic stem cell transplantation (alloHSCT) rates. Panobinostat is a pan-deacetylase inhibitor that increases acetylation of proteins involved in cancer. Preclinical studies in AML demonstrated that panobinostat potentiates the activity of cytarabine (ara-C) and fludarabine and has synergistic activity in combination with doxorubicin in vitro. Single-agent panobinostat has induced CR in patients (pts) with AML. The addition of panobinostat to an active chemotherapeutic regimen in pts with relapsed/refractory AML has the potential to improve therapeutic outcomes in this setting. AIMS: This phase Ib, multicenter, open-label dose-escalation study was designed to determine the maximum tolerated dose (MTD) of panobinostat in combination with a fixed dose of ara-C and mitoxantrone in pts with relapsed/refractory AML. The secondary objectives were to characterize safety and tolerability during the dose-escalation phase and at the MTD and to evaluate anti-leukemic activity. METHODS: Successive cohorts of at least 3 pts with confirmed relapsed or refractory AML were treated with oral panobinostat (starting with 20 mg, escalated in 10-mg steps) thrice weekly on days 1, 3, 5, 8, 10, and 12, in combination with intravenous ara-C (1 g/m2) on days 1–6 and mitoxantrone (5 mg/m2) on days 1–5 of a 28-day cycle. The MTD was determined on the basis of the observed dose-limiting toxicities (DLTs), safety assessment, and tolerability during the first 28 days after starting panobinostat. A DLT was defined as any adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications with the following criteria: neutropenia lasting > 28 days after cycle 1 for hematologic DLTs; grade 4 AST/ALT or grade 3 AST/ALT for > 7 days; grade 3/4 bilirubin, vomiting, diarrhea, or any non-hematologic toxicity for non-hematologic DLTs. Safety and tolerability were described as type, duration, frequency, relatedness, and severity of AEs according to CTCAE v3.0. The adaptive Bayesian logistic regression model was used to guide dose escalation with overdose control. RESULTS: Of 5 dose levels, 40 pts (median age, 55 years; range, 19–73 years) were treated at panobinostat dosages of 20 to 60 mg, with 5 pts at 20 mg, 8 at 30 mg, 10 at 40 mg, 11 at 50 mg, and 6 at 60 mg. Of 6 DLTs observed, 1 was at 40 mg (sepsis and tachyarrhythmia), 2 were at 50 mg (vomiting/nausea; diarrhea), and 3 were at 60 mg (neutropenic colitis; 2 hypokalemic events). Frequent AEs of all grades, regardless of causality, included nausea (32 [80%]), diarrhea (31 [78%]), vomiting (26 [65%]), hypokalemia (25 [63%]), thrombocytopenia (24 [60%]), abdominal pain (22 [55%]), decreased appetite, and febrile neutropenia (21 each [53%]). The most frequent grade 3/4 treatment-related AEs were thrombocytopenia (20 [50%]), anemia (9 [23%]), leukopenia, and neutropenia (7 each [18%]). Serious AEs, regardless of causality, were reported in 23 pts, with febrile neutropenia (12 [30%]) being the most common. The MTD was determined to be 50 mg of panobinostat on the basis of observed DLTs and safety and tolerability in cycle 1 of the dose-escalation phase. Clinical responses were observed in 22 pts (55%), including 13 CR, 5 morphological CR, and 4 partial remissions. In pts receiving 40- and 50-mg doses of panobinostat, the preliminary efficacy was promising, with a response in 11 of 21 pts (52%). An alloHSCT was performed in 8 pts after the start of salvage therapy. CONCLUSIONS: The combination of panobinostat, ara-C, and mitoxantrone showed no unexpected toxicities and promising anti-leukemic activity in pts with relapsed/refractory AML. The MTD was determined to be 50 mg of panobinostat; enrollment at this dose is ongoing for the dose-expansion phase to further assess safety, tolerability, and activity. Thrombocytopenia and anemia were the principal treatment-related hematologic AEs. Treatment-related non-hematologic AEs were primarily gastrointestinal toxicities and fatigue. Disclosures: Krauter: Novartis: Consultancy, Honoraria. Winiger:Novartis AG: Employment, Equity Ownership, Honoraria. Squier:Novartis Corporation: Employment. Zahlten:Novartis AG: Employment. Wang:Novartis Corporation: Employment. Ottmann:Novartis Corporation: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding.
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McBride, Ali, Karen MacDonald, and Ivo Abraham. "Simulation Modeling of Cost-Savings from Conversion to Biosimilar Pegfilgrastim-Cbqv for the Prophylaxis of Chemotherapy-Induced Neutropenia, and Budget-Neutral Expanded Access to Prophylaxis and Anti-Neoplastic Therapy from Derived Cost-Savings in Non-Hodgkin Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 24–25. http://dx.doi.org/10.1182/blood-2020-136810.
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Introduction: Costs of prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) have been reduced in recent years by the approval of several biosimilar filgrastim and pegfilgrastim agents. The savings from conversion to biosimilars can be reallocated to provide expanded access to CIN/FN prophylaxis or anti-neoplastic treatment. To illustrate this, we simulated in a panel of 20,000 non-Hodgkin lymphoma (NHL) patients: 1) the savings that could be realized from CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim with or without on-body injector (PEG/PEG-OBI), 2) a model of expanded access to CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) a model of expanded access to chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP) for NHL from cost-savings achieved from conversion from PEG/PEG-OBI. Methods: Simulation modeling for a panel of 20,000 NHL patients was conducted from the US payer perspective. Medication costs for PEG/PEG-OBI, pegfilgrastim-cbqv, and R-CHOP drugs were calculated in three ways 1) Q1 2020 average selling price (ASP) derived from CMS Q3 2020 reimbursement limits, 2) Wholesale Acquisition Cost (WAC) from Redbook, and 3) a blended ASP/WAC rate proportionate to the NHL age distribution per Surveillance, Epidemiology, and End Results Program data. These three cost estimate bases were applied to one through six cycles of prophylaxis with conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100%. The number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of pegfilgrastim-cbqv or one additional cycle of R-CHOP chemotherapy was also estimated. Results: Using ASP, cost-savings of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI in a panel of 20,000 NHL patients ranged from $371,444 (for 1 cycle of prophylaxis at 10% conversion) to $22,286,640 (6 cycles at 100% conversion). The corresponding savings ranged from $4,112,120 to $246,727,200 when using WAC; and from $1,976,194 to $118,571,640 when using the age-proportionate blended ASP/WAC rate. Focusing on the blended ASP/WAC rate, the savings in a single cycle of chemotherapy translated into expanded access to biosimilar pegfilgrastim-cbqv ranging from 524 cycles at 10% conversion from PEG/PEG-OBI to 5,243 cycles at 100% conversion. The savings over six cycles of biosimilar prophylaxis could provide between 3,146 (at 10% conversion) and 31,457 (at 100% conversion) additional cycles of biosimilar pegfilgrastim-cbqv. The NNC from one cycle of PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv to purchase one additional cycle of biosimilar pegfilgrastim-cbqv is 4. In a single cycle of chemotherapy, savings using the blended ASP/WAC rate translated into expanded access to R-CHOP ranging from 282 cycles at 10% to 2,817 cycles at 100% conversion. The savings over six cycles of biosimilar prophylaxis could provide between 1,690 (at 10% conversion) and 16,900 cycles (at 100% conversion) additional cycles of R-CHOP. The NNC from one cycle of PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv to purchase one additional cycle of R-CHOP is 8. Conclusions: These simulation models demonstrate that significant cost savings for supportive cancer care can be generated through conversion to biosimilar pegfilgrastim-cbqv for CIN/FN prophylaxis. The savings generated from conversion from PEG/PEG-OBI can be reallocated on a budget-neural basis to provide expanded access to additional patients/cycles of CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv or to curative anti-neoplastic treatment. Such efficiency and expanded access enhance the value of cancer care to payers and patients. Disclosures McBride: MorphoSys: Consultancy; Sandoz: Consultancy; Pfizer: Consultancy; Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy. MacDonald:Sandoz: Consultancy; MorphoSys: Consultancy; Celgene: Consultancy; Terumo: Consultancy; Rockwell Medical: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Mylan: Consultancy; Coherus BioSciences: Research Funding. Abraham:MorphoSys: Consultancy; Sandoz: Consultancy; Mylan: Consultancy; Janssen: Consultancy; Rockwell Medical: Consultancy; Terumo: Consultancy; Celgene: Consultancy; Coherus BioSciences: Research Funding, Speakers Bureau.
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Bixby, Dale, Matthew J. Wieduwilt, Luke Paul Akard, H. Jean Khoury, Pamela S. Becker, Edward H. Van Der Horst, William Ho, and Jorge E. Cortes. "A Phase I Study of IGN523, a Novel Anti-CD98 Monoclonal Antibody in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)." Blood 126, no. 23 (December 3, 2015): 3809. http://dx.doi.org/10.1182/blood.v126.23.3809.3809.
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Abstract CD98 is a heterodimeric cell surface protein that is implicated in the pathogenesis of many hematological and solid malignancies. Elevated tumor CD98 expression has been correlated with poor prognosis. Previous studies demonstrated that CD98 functions in integrin signaling and amino acid transport processes that support tumor cell proliferation, anchorage independence, invasion, and metastasis. IGN523 is a humanized monoclonal antibody targeting CD98 with multiple mechanisms of action including antibody-dependent cellular cytotoxicity (ADCC), direct cell death induction, and interference with the normal amino acid transport function of CD98. IGN523 elicits potent anti-tumor activity against a variety of leukemic xenograft models (Hayes et al., Int. J. Cancer 2015). Here we present the results of a Phase I dose escalation study of IGN523 in adult patients with relapsed or refractory AML. IGN523 was administered intravenously (IV) as a single agent to 19 patients at weekly doses ranging from 0.1 mg/kg to 20 mg/kg, including 3 single-patient cohorts starting at 0.1, 0.3, and 1 mg/kg, 6 patients treated at 10 mg/kg, 3 at 20 mg/kg, and 7 at 15 mg/kg. Median age was 71 years (range 23-78). Patients received a median of one 4-week cycle of treatment (range <1-10 cycles). The most common treatment-related adverse events observed were part of infusion-related reactions (IRRs) occurring primarily with the first infusion, and were generally Grade 1 or 2 (CTCAE V4.03), including chills (52.6%), fever (pyrexia or febrile neutropenia, 36.9%), nausea (26.3%), and vomiting (26.3%). Premedication with acetaminophen, diphenhydramine, and hydrocortisone was instituted after a dose-limiting toxicity (DLT) of significant IRR with the first dose was observed in 1 of 3 patients treated at 10 mg/kg, and the cohort was expanded to 6 patients. Treatment-related Grade 3 and 4 AEs occurring in >1 patient included febrile neutropenia (26.1%), pyrexia (10.5%), and altered mental status (confusional state or mental status changes in 15.8% and 10.5% respectively). DLTs all occurred with the first dose of IGN523 and were observed in 1 of 6 patients at 10 mg/kg, 2 of 3 at 20 mg/kg, and 2 of 7 at 15 mg/kg. The maximum tolerated dose (MTD) of IGN523 administered weekly was 10 mg/kg. PK studies of IGN523 in all patients demonstrated evidence of target-mediated drug disposition at doses below 10 mg/kg/week, as pre-dose (trough) CD98 receptor occupancy (%RO) levels tended to be < 90%. By the 10 mg/kg dose cohort, pre-dose %RO levels were 50 to > 90% during the first few weeks of dosing, and consistently > 90% after 4-8 weeks of dosing. At 15 and 20 mg/kg/week doses, %RO was consistently > 90% from the first dose. Therefore, dose levels of 10 mg/kg/week and above should be suitable for most patients to maintain >90% receptor occupancy over time. Anti-drug antibodies (ADA) were not detected in any patient. Evidence of transient anti-leukemic activity was observed in 3 patients, including improvement in platelet count and reduction in marrow blast percentage, early reduction and control of blasts, and an episode of tumor lysis and peripheral blast count reduction. No complete or partial responses were observed. In conclusion, IGN523 was safe when administered at 10 mg/kg IV weekly with DLTs of significant first-dose infusional toxicity that may be manageable with prophylactic steroids or a modified dosing regimen. IGN523 demonstrated modest evidence of anti-leukemic activity as a single agent. Preclinical data demonstrating greater than additive activity of IGN523 when combined with cytarabine and significant monotherapy and combination activity with standard chemotherapy in patient-derived xenograft models of NSCLC and colorectal cancer support further development of IGN523 in combination with standard therapies in AML and solid tumors. Disclosures Bixby: Seattle Genetics, Inc.: Research Funding. Akard:Novartis: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Millenium: Speakers Bureau; Ariad: Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Pfizer: Research Funding; Incyte: Research Funding. Khoury:Pfizer: Honoraria; Ariad: Honoraria; Bristol-Meyer-Squibb: Honoraria. Becker:Igenica: Research Funding. Van Der Horst:Igenica: Employment. Ho:Igenica: Employment. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding; BerGenBio AS: Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.
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Wildiers, Hans, Sandrine Marreaud, Lissandra Dal Lago, Peter Vuylsteke, Giuseppe Curigliano, Simon Waters, Barbara Brouwers, et al. "Abstract P1-18-06: Long term outcome data from the EORTC 75111-10114 ETF/BCG randomized phase II study: Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2- positive metastatic breast cancer, followed by T-DM1 after progression." Cancer Research 82, no. 4_Supplement (February 15, 2022): P1–18–06—P1–18–06. http://dx.doi.org/10.1158/1538-7445.sabcs21-p1-18-06.
Full textAbstract:
Abstract Introduction: Pertuzumab (P) is approved as first line therapy for HER2-positive (HER2+) metastatic breast cancer (MBC) combined with trastuzumab (T) and docetaxel. However older patients are at high risk of chemotherapy-induced toxicity ,raising interest in less toxic anti-HER2 therapy regimens.Patients and Methods: This phase II selection study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide 50 mg/day + TP (TPM) or TP alone. Prior endocrine therapy and up to 1 line of anti-HER2 therapy (without chemotherapy) for MBC were allowed. T-DM1 was offered in case of progression. Randomization was stratified according to hormonal receptors, previous anti-HER2 treatment and geriatric assessment. Primary endpoint was progression-free survival (PFS) rate at 6months, already reported (Lancet Oncol 2018, Wildiers et al). We now present data on long term outcome (including cause of death), and on response and tolerance of T-DM1 given after progression on TP(M).Results: Between July 2013 and May 2016, 39 and 41 patients were randomized to TP and TPM arm respectively: median age 76.7 years, hormone receptor positivity 69%, prior (neo)adjuvant T 11%, prior metastatic T (with endocrine therapy) 3%, visceral involvement 93.7%, potential frailty profile according to geriatric screening G8 (≤14) 70% and/or to short physical performance battery (<10) 81%, Charlson comorbidity score > 0 in 41%. With 54.0 months of median follow-up, 6-month PFS was 43.1% (95% CI 27.1-58.1) versus 73.0% (95% CI 55.8-84.3) for TP and TPM, respectively. 12-month PFS was 33.7% and 51.9%, and 24-month PFS 18.7% and 28.7%, respectively. A total of 49 (61.3%) patients died, 27 (69.2%) in the TP arm and 22 (53.7%) in the TPM arm. There was no significant difference in OS between the two arms (TPM vs TP: HR=0.72, 95% CI 0.41-1.26) with median OS 32.1 months for TP, and 37.5 months for TPM. The causes of death were progressive disease (N=37, 75.5%), toxicity (cardiac failure, N=1, 2.0%), and other causes not due to PD/toxicity (N=9, 22.5%). Among the 40 patients who have started T-DM1 (22 in TPM arm and 18 in TP arm), median follow-up was 33.7 months from T-DM1 start. PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5). Grade 3 or higher AE occurred in 18 pts (45%). Most relevant reported grade III or higher toxicities on T-DM1 were fatigue (N=3), anorexia (N=2), anemia (N=1), febrile neutropenia (N=1), diarrhoea (N=1), hepatic failure (N=1), lung infection (N=1), increased GGT (N=1), thrombocytopenia (N=1), weight loss (N=1), hypophosphatemia (N=1), dyspnoea (N=1), epistaxis (N=1), hematoma (N=1). Two patients (5%) experienced grade 5 toxicity: one death was considered as related to cachexia and tumor progression; the other death was considered to be related to acute pneumonia and renal failure. The prognostic impact of geriatric assessment on PFS and OS, and frailty evolution during therapy will be presented at the meeting.Conclusions: Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years despite the associated frailty in the majority of the study population. T-DM1 provides a PFS rate at 6 months of 43.6% (95% CI: 27.7-58.5) with a wide range of possibly related toxicities in this generally frail population. Citation Format: Hans Wildiers, Sandrine Marreaud, Lissandra Dal Lago, Peter Vuylsteke, Giuseppe Curigliano, Simon Waters, Barbara Brouwers, Bart Meulemans, Berta Sousa, Coralie Poncet, Etienne Brain. Long term outcome data from the EORTC 75111-10114 ETF/BCG randomized phase II study: Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2- positive metastatic breast cancer, followed by T-DM1 after progression [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-06.