Journal articles on the topic 'Taxane-based therapy'
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Sparano, Joseph A., and Lakshmi Rajdev. "Taxane-Based Therapy for Breast Cancer: Combination or Sequential Therapy?" Cancer Investigation 18, no. 5 (January 2000): 498–500. http://dx.doi.org/10.3109/07357900009032823.
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Dwipoyono, Bambang, Septyana Choirunisa, Mardiati Nadjib, and Amal C. Sjaaf. "COST ANALYSIS OF TAXANE-BASED AND CISPLATIN-BASED CHEMOTHERAPY REGIMENS FOR EPITHELIAL OVARIAN CANCER IN DHARMAIS NATIONAL CANCER HOSPITAL." International Journal of Applied Pharmaceutics 9 (October 30, 2017): 172. http://dx.doi.org/10.22159/ijap.2017.v9s1.82_89.
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Objective: This exploratory study aimed to evaluate and compare the treatment costs of taxane-based versus cisplatin-based chemotherapy.Methods: This study used data from the medical and financial records of ovarian cancer patients who were admitted to Dharmais NationalCancer Hospital (RSKD) between 2008 and 2012 and subsequently underwent surgery and were treated with chemotherapy. Data were analyzedusing descriptive analysis, and a Kaplan–Meier graph was plotted to compare the survival of the patients in the taxane-based and cisplatin-basedchemotherapy groups.Results: Of 41 patients, treatment costs were available for nine patients who had undergone taxane-based chemotherapy and for 31 patients who hadundergone cisplatin-based chemotherapy. In general, surgical procedures accounted for the highest proportion of the treatment costs, followed bychemotherapy. Taxane-based chemotherapy (six cycles) was 4 times more expensive than cisplatin-based therapy. The pre- and post-chemotherapycosts of care among those treated with the taxane-based regimen were 3-4 times more expensive than those of the patients who received cisplatinbasedtreatment. The disease-free recurrence duration of the patients treated with taxane was longer (median=18 months) than that of the patientstreated with cisplatin (median=5 months).Conclusions: Taxane-based therapy increased the disease-free recurrence duration of the patients, with disease-free recurrence 3 times longer thanthat of the patients treated with the cisplatin-based regimen. However, the treatment costs of the taxane-based regimen were 4 times higher thanthose of the cisplatin-based treatment.
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Piccart-Gebhart, M. J., and P. L. Bedard. "Who benefits from taxanes?" Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e11503-e11503. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e11503.
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e11503 Over the last fifteen years, 21 clinical trials randomized nearly 36,000 women with early-stage breast cancer to taxane-based versus non-taxane-based adjuvant chemotherapy regimens to establish the role of taxanes in early breast cancer therapy. Preliminary results from the Oxford Overview –pooling individual patient data from some of these studies –suggest that the inclusion of a taxane to an anthracycline-based regimen reduces 10-year breast cancer related mortality by an absolute value of 5% over anthracycline therapy alone. In spite of this enormous global research effort, there remains considerable uncertainty regarding which patients benefit from taxane therapy. Three recent meta-analyses indicate that taxanes are beneficial irrespective of age, lymph node involvement, and hormonal receptor expression. Unfortunately, differences in trial design, pathological evaluation, and outcome reporting limit the robustness of these findings. Individual studies have suggested that patients with HER-2 positive disease derive greater benefit from taxane therapy, although the methods used to assess HER-2 status have been heterogeneous and there is no clear biological rationale to account for differential benefit in this subset. A number of promising predictive molecular markers related to taxane metabolism, microtubule dynamics, and intracellular signaling warrant further evaluation using biospecimens collected from the first-generation taxane trials. Future clinical trials should account for the molecular heterogeneity of breast cancer, by excluding the chemotherapy insensitive luminal A subset and mandating upfront central pathological assessment to further optimize the role of taxane therapy in early-stage disease. No significant financial relationships to disclose.
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&NA;. "Abdominal pain may signal colitis in taxane-based therapy." Inpharma Weekly &NA;, no. 1461 (October 2004): 17. http://dx.doi.org/10.2165/00128413-200414610-00040.
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&NA;. "Abdominal pain may signal colitis in taxane-based therapy." Reactions Weekly &NA;, no. 1025 (October 2004): 5. http://dx.doi.org/10.2165/00128415-200410250-00009.
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Armstrong, Andrew J., Jun Luo, Monika Anand, Emmanuel S. Antonarakis, David M. Nanus, Paraskevi Giannakakou, Russell Zelig Szmulewitz, et al. "AR-V7 and prediction of benefit with taxane therapy: Final analysis of PROPHECY." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 184. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.184.
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184 Background: We previously found that men with AR-V7 (+) poor risk mCRPC have a low chance of benefit with abiraterone or enzalutamide. The benefits of subsequent taxane chemotherapy based on AR-V7 status may help inform treatment decisions. Methods: We conducted a multicenter prospective study of men with poor risk mCRPC (PROPHECY, NCT02269982) starting Abi or Enza and subsequent taxane chemotherapy. AR-V7 status from CTCs was assessed before abi/enza and again before taxane chemotherapy using the Epic nuclear protein assay or the Johns Hopkins Adnatest assay. The primary endpoint was to test the association of AR-V7 with radiographic/ clinical progression free survival (PFS) and OS with taxane chemotherapy, using the proportional hazards model, adjusting for Cell Search enumeration and clinical risk score. Results: We enrolled 118 men with mCRPC starting Abi/Enza; of these, 51 were evaluable with CTC AR-V7 testing and received subsequent taxane chemotherapy. With 50 PFS events, see table for final results. While AR-V7 positivity was associated with worse outcomes overall, AR-V7 (+) patients had similar PFS, OS, and confirmed >50% PSA declines adjusting for CTC enumeration and clinical prognostic factors. Concordance between the two AR-V7 assays pre-taxane was 0.78 (kappa 0.46). AR-V7 positivity increased at progression on abi/enza, but not following taxane chemotherapy. Conclusions: Men with AR-V7 positive mCRPC have poor outcomes, but may benefit from taxane chemotherapy after progression on abi/enza. AR-V7 may provide a helpful predictive biomarker to guide treatment with a second AR inhibitor or a taxane. Clinical trial information: NCT02269982. [Table: see text]
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Laino, Charlene. "Adding Taxane to Anthracycline-Based Therapy Does Not Improve Outcomes." Oncology Times 30, no. 12 (June 2008): 37–39. http://dx.doi.org/10.1097/01.cot.0000326170.34970.c4.
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Chelala, Elias, Nicolas Arej, Joelle Antoun, Hampig Raphael Kourie, Karen Zaarour, Fady Ghassan Haddad, Fadi Farhat, Fadi El Karak, and Joseph Kattan. "Central Macular Thickness Monitoring after a Taxane-Based Therapy in Visually Asymptomatic Patients." Chemotherapy 62, no. 3 (2017): 199–204. http://dx.doi.org/10.1159/000456653.
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Background: Taxanes are drugs used in various chemotherapeutical protocols to treat solid tumors. They have multiple systemic adverse effects, such as bone marrow suppression, alopecia, nausea, and vomiting, and may rarely cause ocular symptoms. In the past decade, a few reported cases have shown the occurrence of a cystoid macular edema with significant visual loss after the use of a taxane-based chemotherapy. The aim of this study was to compare the central macular thickness (CMT) before and after the initiation of a taxane-based therapy in visually asymptomatic patients and to elucidate the possible impact of these drugs on the vision of cancer patients. Methods: Patients with a confirmed diagnosis of a solid tumor were screened for any ophthalmic disease before inclusion and had a baseline macular spectral domain optical coherence tomography (OCT; RTVue-100; Optovue Inc., Fremont, CA, USA) before the initiation of a taxane-based chemotherapy according to different protocols, such as 4EC-4T, 3FEC/3T, or 4TC. OCT was repeated after 4 cycles (or 3 months) of treatment, and CMT was compared to baseline. Patients presenting diabetic retinopathy, age-related macular degeneration or any condition that causes macular edema confirmed by ophthalmic examination were excluded. Results: Fifty eyes of 25 patients were included; 92% of the subjects were female with a mean age of 48.52 years, 88% were diagnosed with breast cancer, 8% with esophageal cancer, and 4% with ovarian cancer. Docetaxel was the taxane administered to 92% of the patients. The received dose of docetaxel ranged between 110 and 160 mg. The other patients had paclitaxel in their protocols. No significant macular edema or drop in visual acuity were noted in any patient. Nevertheless, the mean CMT was found to be increased, particularly in the parafoveal and perifoveal areas (mean difference of +2.22 μm; p = 0.001). Conclusion: Taxane-based chemotherapy regimens seem to increase macular thickness, with a relative sparing of the fovea, in patients without significant macular edema. Further research is required to better explain the pathophysiology and possible impact of this phenomenon.
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Higano, Celestia S., Lauren C. Harshman, Sabina Dizdarevic, John Logue, Timothy Richardson, Saby George, Danny Song, et al. "Safety and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) plus subsequent taxane therapy." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 5542. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5542.
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5542 Background: Ra-223, a targeted alpha therapy, showed a survival benefit and favorable safety profile over 3 years’ (yrs) follow-up in mCRPC pts (ALSYMPCA trial). REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of long-term Ra-223 safety in routine clinical practice in mCRPC pts (planned 7-yr follow-up). Methods: This analysis, based on the second prespecified interim analysis (data cutoff 3-20-2019) of REASSURE (N = 1465), evaluated safety/OS in the pt subset that was chemotherapy-naïve at Ra-223 administration but received subsequent taxane therapy any time after Ra-223 completion. Results: 182 pts received taxane therapy after Ra-223. Most (58%) had unresected primary tumors, 69% had ≥6 metastases, 99% received prior systemic anticancer therapy (Table). 143 (79%) completed 5 or 6 Ra-223 injections. Subsequent anticancer therapies included docetaxel (95%), enzalutamide (25%), cabazitaxel (24%), abiraterone (12%), lutetium-177-prostate-specific membrane antigen (4%), and sipuleucel-T (1%). During/up to 30 days after taxane therapy, 15 pts (8%) had grade 3/4 hematologic adverse events: anemia (erythropenia) (n = 11, 6%), neutropenia (n = 3, 2%), and thrombocytopenia (n = 2, 1%). Median OS was 24.3 (95% CI: 20.9–27.5) months from Ra-223 initiation and 11.8 (95% CI: 10.6–14.1) months from subsequent taxane initiation. Conclusions: In this cohort where Ra-223 was integrated prior to taxane therapy, most pts received multiple subsequent anticancer therapies. It appears that sequencing of multiple treatment modalities with different mechanisms of action may contribute to improved OS. Taxane therapy in routine clinical practice in pts previously treated with Ra-223 had acceptable hematologic safety/tolerability profiles. Clinical trial information: NCT02141438 . [Table: see text]
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moloney, carolyn, Sue Sukor, Michael Thomas McCarthy, and Cliona Grant. "A review of head and neck squamous cell carcinoma response to taxane chemotherapy treatment in the pre versus post nivolumab era." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e18504-e18504. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e18504.
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e18504 Background: Nivolumab received FDA approval as monotherapy for the treatment of recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck after failure of platinum-based therapy in 2016. This approval was based on CheckMate 141. When patients ultimately relapse after immunotherapy in the second line setting, third line agents include single agent or combination treatment with a Taxane. Methods: We identified patients with metastatic or recurrent squamous cell head and neck cancer in an Irish hospital who had received Taxane chemotherapy after immunotherapy. We looked at outcomes for these patients including progression free survival (PFS) and overall survival (OS). We then identified a group of patients who received a Taxane following platinum failure in the pre-Nivolumab era to act as a comparator. Our objective was to compare PFS and OS to subsequent Taxane chemotherapy in the era before and after the introduction of Nivolumab as a therapy for platinum refractory head and neck SCC. Results: This retrospective cohort study was made up of 26 patients with metastatic or recurrent head and neck cancer. Primary sites included oropharynx, oral cavity, larynx and nasal cavity squamous cell cancers. The patients had a median age of 56. 13 of these patients identified had progressed on Nivolumab but remained fit for a next line of treatment. Median PFS in this group on Taxane based chemotherapy in the third line setting was 3.8 months. Median OS post progression on Nivolumab was 10 months. One patient remarkably had a complete response to Paclitaxel chemotherapy after progression on previous lines of treatment including immunotherapy, platinum chemotherapy and radiotherapy. We then identified a group of 13 patients with metastatic or recurrent head and neck cancer that had progressed on platinum based therapy in the era before Nivolumab was available. Median PFS after Taxane second line chemotherapy was 2.2 months. Median OS in this group after progressing on platinum treatment was 5.8 months. Conclusions: We set out to share our experience of real-world outcomes for head and neck cancer patients in the Nivolumab era. We found that our patients have shown to have an improved overall survival benefit with subsequent Taxane chemotherapy after immunotherapy compared to those who have not received immunotherapy. All fit patients should be considered for Taxane therapy post failure of Nivolumab.
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Agarwal, Neeraj, Simon Chowdhury, Anders Bjartell, Byung Ha Chung, Andrea Juliana Pereira de Santana Gomes, Robert W. Given, Álvaro Juárez Soto, et al. "Time to second progression (PFS2) in patients (pts) from TITAN with metastatic castration-sensitive prostate cancer (mCSPC) by first subsequent therapy (hormonal vs. taxane)." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 82. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.82.
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82 Background: TITAN, a phase 3, randomized, double-blind study of apalutamide (APA) vs placebo (PBO) added to androgen deprivation therapy (ADT), demonstrated significant improvement in radiographic progression-free survival and overall survival in a broad pt population with mCSPC who received APA (Chi KN et al. NEJM 2019). This post hoc analysis evaluates whether type of 1st life-prolonging subsequent therapy (hormonal vs taxane) has an effect on PFS2 benefit shown with APA + ADT. Methods: PFS2 (the time from randomization to disease progression on 1st subsequent therapy for prostate cancer or death, whichever occurs first) was evaluated for pts from TITAN based on 1st subsequent life-prolonging therapy (hormonal vs taxane) after study treatment. Analysis censored all other 1st subsequent systemic therapies after start of treatment. Results: 277 pts (APA, 87; PBO, 190) received subsequent systemic therapy for prostate cancer; 86 pts (APA, 24; PBO, 62) received hormonal therapy (abiraterone acetate + prednisone or enzalutamide) and 99 (APA, 30; PBO, 69) received taxane (docetaxel or cabazitaxel) as 1st subsequent therapy. Baseline demographic and disease characteristics were generally similar between groups. The taxane group had a higher proportion of pts with high volume and pts with > 10 bone metastases, and a lower proportion with prior docetaxel exposure when compared with the hormonal group. Median treatment duration with APA and PBO was 11.9 and 11.1 mos in the hormonal group and 11.0 and 11.3 mos in the taxane group. Regardless of subsequent therapy, PFS2 was significantly longer for APA vs PBO (HR 0.66 [95% CI 0.50-0.87], p = 0.0026). Pts in both groups who received APA had a significant reduction in risk of 2nd progression compared with PBO (hormonal: HR 0.68 [0.48-0.97], p = 0.0326; taxane: HR 0.67 [0.48-0.94], p = 0.0189; medians not reached). Safety analyses were not conducted; all pts had discontinued therapy, most due to disease progression. Conclusions: The addition of APA to ADT for treatment of mCSPC results in risk reduction of 2nd progression regardless of choice of hormonal or taxane as the 1st life-prolonging subsequent therapy. Clinical trial information: NCT02489318.
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Deng, Shanshan, Raisa I. Krutilina, Deanna Parke, Hao Chen, Duane D. Miller, Wei Li, and Tiffany Nicole Seagroves. "VERU-111: An Oral Tubulin Inhibitor That Suppresses Taxane-Sensitive and Taxane-Resistant Breast Cancer." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A1035. http://dx.doi.org/10.1210/jendso/bvab048.2118.
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Abstract Triple negative breast cancer (TNBC) patients have poorer overall prognosis relative to patients diagnosed with other molecular subtypes due to rapid onset of drug resistance to conventional chemotherapies and increased risk of visceral metastases. The microtubule inhibitor paclitaxel (Taxol, a taxane) is a frontline therapy for advanced breast cancer. We evaluated in TNBC models the preclinical safety and efficacy of a novel, potent, and orally bioavailable tubulin inhibitor, VERU-111, a tubulin inhibitor targeting the colchicine binding site. VERU-111 showed potent anti-proliferative and anti-migratory activity against several taxane-sensitive and taxane-resistant TNBC breast cancer cell lines. Based on these observations, taxane-resistant HER2+ cell lines were generated, and were also found to be responsive to VERU-111 treatment. In vivo, orally administered VERU-111 inhibited MDA-MB-231 tumor growth in a dose-dependent manner with antitumor potency similar to paclitaxel, and repressed metastases originating from the mammary fat pad or following tail vein injection. In contrast, in a MDA-MB-231 paclitaxel-resistant (TxR) subline, tumor growth was refractory to paclitaxel whereas VERU-111 significantly inhibited primary tumor growth and reduced lung and liver metastases. VERU-111 was then tested in a luciferase-labeled, multidrug resistant patient-derived xenograft (PDX) TNBC model. VERU-111 significantly inhibited HCI-10 PDX tumor growth and suppressed the expansion of axillary lymph node metastases present prior to initiation of therapy while suppressing lung, liver, bone and kidney metastases at study endpoint. Moreover, in contrast to paclitaxel, VERU-111 therapy did not cause a significant decrease in mouse body weight during treatment. Evaluation of efficacy of VERU-111 in taxane-sensitive and -resistant HER2+ xenograft models is in progress. Overall, we conclude that VERU-111 is a new generation orally bioavailable tubulin inhibitor that potently inhibits the growth of taxane-sensitive and taxane-resistant breast cancers with reduced adverse side effects relative to paclitaxel. Importantly, VERU-111 is well-tolerated in patients as evaluated in phase I/II clinical trials for advanced prostate cancer patients (NCT03752099). We propose that VERU-111 will be an effective second line therapy for patients with advanced breast cancer who progress on taxane-based therapeutic regimens.
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Al-Ezzi, Esmail Mutahar, Jamila Jama Almi Riromar, Eitan Amir, Rouhi Fazelzad, and Aaron Richard Hansen. "Cross-trial comparison of taxane versus non-taxane combination chemotherapy regimens for advanced penile cancer (APC): A systematic review." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 511. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.511.
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511 Background: Penile cancer is rare and there are scant data on the optimal chemotherapy regimen. The majority of trials are single arm, non-randomized studies. Here we report on a systematic review aiming to compare taxane combination chemotherapy regimens with non-taxane regimens for APC. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. Medline, Embase and Cochrane Central Register of Controlled Trials databases were searched using the following terms: penile cancer, penis, antineoplastic combined chemotherapy, taxane, docetaxel, paclitaxel, platinum, cisplatin, carboplatin. Studies were identified using preplanned eligibility criteria by 2 investigators (EA-E and JR). Data were extracted independently by EA-E and JR. Studies were weighted by study sample size and those comparing taxane-based chemotherapy were compared to non-taxane therapy using the Mann Whitney test. Results: The search identified 1929 publications and 40 were selected for further assessment. Of these, 8 met eligibility criteria (7 prospective and 1 retrospective). Three studies tested taxane combinations (docetaxel, cisplatin and 5FU [DCF] and paclitaxel, ifosfamide and cisplatin [TIP]). A total of 148 men with APC were treated with non-taxane regimens and 98 men received a taxane combination. Patient characteristics (age, ECOG status, stage, number of cycles) were comparable between the two groups. Partial response and overall response rates were significantly higher in the taxane versus the non-taxane group (35.7% vs. 24.2% p = 0.01 and 41.9% vs. 32.5% p = 0.007) respectively. Grade3/4 neutropenia was significantly higher in taxane group than non-taxane group (27.8% vs 19.4% p = 0.02). Median PFS and OS was numerically but not significantly higher in the taxane versus the non-taxane group (5.7 vs. 4.4 months, p = 0.45 and 12.1 vs 10 months, p = 0.48, respectively). Conclusions: Compared to non-taxane-based regimens, taxane combinations have higher response rates and may improve survival in APC. Hematologic toxicities are worse with taxane containing regimens. Taxane combinations should be the preferred regimen for suitable men with APC.
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Sonpavde, Guru, Gregory Russell Pond, Giuseppe di Lorenzo, Carlo Buonerba, Antonio Rozzi, Gaetano Lanzetta, Andrea Necchi, et al. "Impact of prior platinum on patients receiving salvage systemic therapy for advanced urothelial carcinoma (UC)." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 386. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.386.
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386 Background: Trials of salvage therapy for advanced UC have required prior platinum-based therapy. This practice requires scrutiny since non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients (pts). We examined the impact of prior exposure to first-line platinum vs. non-platinum based chemotherapy on overall survival (OS) with salvage systemic chemotherapy. Methods: Data of pts receiving salvage systemic chemotherapy were collected retrospectively or from trials. Data on prior first-line platinum exposure were required in addition to the known prognostic factors: treatment free interval, hemoglobin, performance status, albumin and liver metastasis status. Cox proportional hazards regression was used to evaluate their association with OS after accounting for salvage therapy with single agent chemotherapy or combination chemotherapy. Results: Data was obtained from 455 pts exposed to prior platinum and 37 pts not exposed to prior platinum. In the group exposed to prior platinum, salvage therapy consisted of a single agent taxane (n = 184) and taxane containing combination chemotherapy (n = 271). In the group not exposed to prior platinum, salvage therapy consisted of single agent taxane or vinflunine (n = 20), single agent 5-fluorouracil (n = 1), taxane containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2) and cisplatin-based combinations (n = 2). The median OS for the prior platinum group was 7.8 (95% CI: 7.0, 8.1) months (mo), and for the prior non-platinum group was 9.0 (6.0, 11.0) mo (p = 0.50). In a multivariable analysis including major prognostic factors and after controlling for single agent or combination salvage chemotherapy, prior platinum vs. no prior platinum exposure conferred no independent impact on OS (HR 1.10 [0.75, 1.64], p = 0.62). Conclusions: Prior platinum vs. non-platinum based chemotherapy did not confer a prognostic impact on OS after accounting for major prognostic factors in pts receiving salvage systemic chemotherapy for advanced UC. Lack of exposure to prior platinum should not disqualify pts from inclusion in trials of salvage therapy after accounting for the 5 known prognostic factors.
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Cecchi, Fabiola, Daniel V. T. Catenacci, Yuan Tian, Rosalba Miceli, Filippo Pietrantonio, Alessandro Pellegrinelli, Antonia Martinetti, Maria Di Bartolomeo, and Todd A. Hembrough. "Quantitative proteomic analysis of TUBB3 to identify gastric cancer patients who may benefit from docetaxel: A reevaluation of the ITACA-S trial." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 59. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.59.
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59 Background: Chemotherapy (CTX) becomes targeted therapy when biomarkers can predict a patient’s response. A relationship between resistance to taxanes and overexpression of class III b-tubulin (TUBB3) has been suggested by small clinical studies, but not confirmed in randomized trials. The Intergroup Trial of Adjuvant CTX in Adenocarcinoma of the Stomach (ITACA-S) evaluated the survival advantage of postoperative sequential CTX with FOLFIRI followed by docetaxel plus cisplatin in comparison to monotherapy with 5-FU/LV in patients with radically resected gastric cancer (N = 1106). The results showed no difference in survival between the two CTX arms. In a random subset of patients (N = 247) from the ITACA-S trial, we applied mass spectrometry-based proteomics to assess the role of TUBB3 as a predictive biomarker for response to taxane-containing therapy. Methods: Archived tumor tissues were microdissected and solubilized for proteomic analysis. TUBB3 and 44 other protein biomarkers were quantified using a mass spectrometry-based selected reaction monitoring assay. A predetermined TUBB3 cutoff of 700 amol/µg was based on the assay’s limit of detection. The Mantel-Cox log-rank test was used for survival comparisons. Results: Among patients treated with taxane-containing CTX (n = 125), those with TUBB3 levels below the cutoff had nearly twice the median overall survival (OS) as patients with TUBB3 levels above the cutoff (1566 vs. 801 days, p = 0.0282). TUBB3 levels made no statistical difference in survival among patients who did not receive taxane. Of note, among patients with high TUBB3 levels ( > 700 amol), those treated without taxane-containing CTX survived far longer than patients in the taxane arm (OS = 1991 vs 801 days, p = 0.048). Conclusions: Quantitative proteomic analysis of TUBB3 expression identified a subset of gastric cancer patients who benefitted from the addition of docetaxel to adjuvant CTX. Patients with high TUBB3 expression levels had worse outcomes on a taxane-containing regimen than on CTX without taxane. Personalized CTX based on the TUBB3 biomarker is promising and warrants further validation. Clinical trial information: NCT01989858.
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Gitlitz, B. J., A. M. Davies, C. P. Belani, A. Argiris, S. S. Ramalingam, P. C. Hoffman, M. Koczwas, S. G. Groshen, and D. R. Gandara. "A phase II study of the halichondrin B analog, E7389, in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane. A California Consortium/University of Pittsburgh/University of Chicago NCI/CTEP sponsored trial." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8056. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8056.
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8056 Background: E7389 is a structurally simplified synthetic macrocyclic ketone analog of halichondrin B and has a unique mechanism of microtubule binding and interaction, distinct from other agents in this class. Thus, it was our hypothesis that pts with prior taxane based therapy would respond to this agent. We conducted a phase II trial of E7389 in prior taxane-treated NSCLC pts. Methods: Eligible pts included: histologically confirmed advanced NSCLC, previous treatment with platinum-based therapy and a taxane, no more than 2 prior regimens, measurable disease, Zubrod performance status ≤ 2. Pts were classified by taxane-sensitivity status: taxane sensitive (TS) (progression >90 days after taxane) or taxane resistant (TR) (progression during or ≤90 days after taxane). Treatment: E7389 1.4 mg/m2 intravenously over 1–2 minutes on day 1 and 8 of a 21 day schedule until disease progression or unacceptable toxicity. Results: 41 pts were entered. There were 3 (15%) objective responses (7.2+, 8.5+, 10.6 mo) of 20 TS pts; and no response of 21 TR pts. Stable disease rate was 60% and 24% in TS and TR pts. respectively. Median progression free survival (PFS) is 6.3 mos TS pts. 95%CI (2.5–8.6 mos) and 1.2 mos TR pts. 95%CI (1.1–4.1 mos). Median number of cycles (range): TS 4 (1–14); TR 2 (1–7). Major toxicity included: 19 pts (46%) with grade 3 or 4 hematologic toxicity including only 1 episode of febrile neutropenia and 8 pts (20%) with grade 3 or 4 non-hematologic toxicity attributable to drug including: fatigue (1), dehydration (2), nausea (2), constipation (2). Only 1 pt developed grade 3 neuropathy (course 9). Conclusions: E7389 was well tolerated with encouraging objective response, PFS and disease control rate in the TS cohort. This cohort will be expanded, using a 2-stage design, to accrue up to another 25 pts. No significant financial relationships to disclose.
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Varayathu, Hrishi, Hephzibah Sara Mathew, Vinu Sarathy, Beulah Elsa Thomas, Santosh Elluru Kumar, Nitheesha Reddy, Suhail Sayeed Mufti, et al. "Taxane induced pulmonary toxicity in breast cancer." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15522-e15522. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15522.
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e15522 Background: Taxanes are an integral part of chemotherapy for a broad range of tumor types. The usual toxicities associated with Taxane use are peripheral neuropathy, myelosuppression and musculoskeletal adverse effects. Very few studies have reported taxane induced pulmonary toxicity objectively. In our study we explored Taxane induced pulmonary toxicity based on discrete CT findings. Methods: 40 non-smokers diagnosed with Her-2 negative breast cancer who received Taxane monotherapy from 2017 to 2018 were retrospectively analyzed for pre and post therapy CT changes. Following CT findings were considered significant as pulmonary toxicity; (a) Nonspecific area with ground-glass attenuation, (b) multifocal areas of airspace consolidation, (c) patchy distribution of ground-glass attenuation accompanied by interlobular septal thickening and (d) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. The CT findings were assessed independently by two radiologists and one pulmonologist. Results: Our study showed that 5 patients (12.5%) developed pulmonary changes on chest CT post Taxane therapy as summarized in Table. Conclusions: Our study shows that taxane has more potential to induce pulmonary toxicity than reported in present literature. Given that taxanes are the most widely used chemotherapy, it is of utmost necessity to be cognizant of this under-reported potentially fatal adverse effect in a large population. Further studies should be conducted to better understand the true potential, mechanisms and patterns of taxanes induced pulmonary toxicity. [Table: see text]
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Freedman, Rachel A., Ines Maria Vaz Duarte Luis, Nancy Lin, Joyce Lii, Eric P. Winer, and Nancy Lynn Keating. "Completion of adjuvant trastuzumab for older patients with early-stage breast cancer (BC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 616. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.616.
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616 Background: Few data are available about factors associated with completion of adjuvant trastuzumab in older women with BC. We examined rates and predictors of adjuvant trastuzumab completion for older women with early-stage BC. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify 1,319 patients ≥66 years with early-stage BC diagnosed between 1999-2007 who received trastuzumab. Completion of trastuzumab was defined as >270 days of therapy. We examined patient, clinical and geographic characteristics associated with trastuzumab completion using multivariable logistic regression. We also assessed rates of hospital admissions for cardiac events during treatment. Results: Most of the 1,319 women were aged ≤76 (70%) and had a comorbidity score=0 (88%); 37% and 23% received anthracyline-taxane-based and taxane-based therapy, respectively, and 16% received trastuzumab without chemotherapy. Overall, 982 women (74.5%) completed trastuzumab. Factors associated with completion are shown below. During treatment, 56 patients (4.2%) had 65 hospital admissions for cardiac events (3.0% in those who completed trastuzumab versus 8.0% in those who did not, p<.001). Conclusions: One-quarter of older patients who initiated adjuvant trastuzumab did not complete therapy. Older women, Hispanic women, those with more comorbidity, and those receiving anthracycline-taxane-based chemotherapy all had lower odds of completion. Rates of hosptializations for cardiac events were higher in those who did not complete therapy. [Table: see text]
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Maxwell, Cathy. "Quality-of-Life Considerations With Taxane-Based Therapy in Metastatic Breast Cancer." Clinical Journal of Oncology Nursing 17 (January 29, 2013): 35–40. http://dx.doi.org/10.1188/13.cjon.s1.35-40.
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Aldrich, Jeffrey D., Kanwal Pratap Singh Raghav, Gauri R. Varadhachary, Robert A. Wolff, and Michael J. Overman. "Retrospective analysis of taxane-based therapy in advanced small bowel adenocarcinoma (SBA)." Journal of Clinical Oncology 36, no. 15_suppl (May 20, 2018): e16263-e16263. http://dx.doi.org/10.1200/jco.2018.36.15_suppl.e16263.
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Bottsford-Miller, Justin, Hyun-Jin Choi, Heather J. Dalton, Rebecca L. Stone, Min Soon Cho, Monika Haemmerle, Alpa M. Nick, et al. "Differential Platelet Levels Affect Response to Taxane-Based Therapy in Ovarian Cancer." Clinical Cancer Research 21, no. 3 (December 3, 2014): 602–10. http://dx.doi.org/10.1158/1078-0432.ccr-14-0870.
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Ota, Shuji, Takahiko Sakamoto, Ryosuke Ochiai, Terunobu Haruyama, Masashi Ishihara, Maika Natsume, Yoko Fukasawa, et al. "Successful Treatment with Taxane-Based Chemotherapy in Advanced Sebaceous Carcinoma: A Case Report and Literature Review." Case Reports in Oncology 12, no. 1 (January 11, 2019): 47–52. http://dx.doi.org/10.1159/000493850.
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For sebaceous carcinoma (SC), a rare malignant tumor, no standard chemotherapy regimen for patients with distant metastasis has been studied. We experienced a case of eyelid SC with multiple lung metastases that responded to combination chemotherapy with carboplatin and paclitaxel with 11-month progression-free survival (PFS). This patient also responded to second-line treatment with docetaxel, another taxane, with 7-month PFS, resulting in at least 18 months of survival at the time of reporting. This report shows that taxane-based chemotherapy may be effective for advanced SC, for which no standard therapy has been established.
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Yee, Samantha S., and April L. Risinger. "Efficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models." Molecules 26, no. 13 (July 3, 2021): 4077. http://dx.doi.org/10.3390/molecules26134077.
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Ovarian cancer often has a poor clinical prognosis because of late detection, frequently after metastatic progression, as well as acquired resistance to taxane-based therapy. Herein, we evaluate a novel class of covalent microtubule stabilizers, the C-22,23-epoxytaccalonolides, for their efficacy against taxane-resistant ovarian cancer models in vitro and in vivo. Taccalonolide AF, which covalently binds β-tubulin through its C-22,23-epoxide moiety, demonstrates efficacy against taxane-resistant models and shows superior persistence in clonogenic assays after drug washout due to irreversible target engagement. In vivo, intraperitoneal administration of taccalonolide AF demonstrated efficacy against the taxane-resistant NCI/ADR-RES ovarian cancer model both as a flank xenograft, as well as in a disseminated orthotopic disease model representing localized metastasis. Taccalonolide-treated animals had a significant decrease in micrometastasis of NCI/ADR-RES cells to the spleen, as detected by quantitative RT-PCR, without any evidence of systemic toxicity. Together, these findings demonstrate that taccalonolide AF retains efficacy in taxane-resistant ovarian cancer models in vitro and in vivo and that its irreversible mechanism of microtubule stabilization has the unique potential for intraperitoneal treatment of locally disseminated taxane-resistant disease, which represents a significant unmet clinical need in the treatment of ovarian cancer patients.
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Howell, Anthony, and Andrew M. Wardley. "Overview of the impact of conventional systemic therapies on breast cancer." Endocrine-Related Cancer 12, Supplement_1 (July 2005): S9—S16. http://dx.doi.org/10.1677/erc.1.01003.
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Survival in women with breast cancer is improving in the western world, in part related to improved surgery, radiotherapy and adjuvant systemic therapy. Aromatase inhibitors are superior to tamoxifen in this clinical situation and several studies indicate that taxane-based chemotherapy is superior to non-taxane-based regimens. Herceptin is active alone in HER-2/neu +ve advanced breast cancer and four clinical trials are testing this agent in the adjuvant situation. It seems likely that herceptin will add to conventional therapies and thus will be the paradigm for the introduction of other biological therapies to improve cure rates.
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Ueno, N. T., S. Kim, W. F. Symmans, M. A. Detry, L. Pusztai, L. F. Sanchez, H. Ishihara, G. N. Hortobagyi, and S. Noguchi. "Prospective study of changes in spindle assembly checkpoint (SAC) to predict breast tumor response to taxanes." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 586. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.586.
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586 Background: Increased cyclin-dependent kinase 1 (CDK1) and reduced CDK2 activity reflects taxane chemosensitivity via regulation of SAC. Novel C2P device (Sysmex Inc.) measures CDK1/2 activity in human tissue within a few hours. We hypothesized that SAC functionality in breast cancer predicts taxane sensitivity. Methods: Biopsy samples obtained before preoperative therapy from 69 pts with primary breast cancer (median age 52, St II, 56%, St III, 40%, HER2 36%, HR 52%) ex vivo with paclitaxel (100 nM) for 24 h, then measured for CDK1/2 activity. Tumors with CDK1/2 ratio > 0.7 were denoted “responders” (CR, PR) based on preclinical testing. Clinical responses were evaluated with sonography. Results: 24 pts could not be evaluated because of unmeasurable or invalid CDK (n=3), no receipt of taxane (n=10), incomplete treatment/lack of imaging (n=10), or receipt of taxane as adjuvant therapy (n=1). Among the 45 evaluable pts, 30 obtained reading to determine the C2P-predicted response, which was significantly associated with the clinical response to preoperative therapy with paclitaxel, docetaxel, docetaxel/doxorubicin, paclitaxel/trastuzumab or lapatinib, or docetaxel/capecitabine (P=0.002; sensitivity 0.83; specificity 0.86; positive predictive value [PPV] 0.95; and negative predictive value [NPV] 0.60). For HER2- tumors, the sensitivity was 0.94; specificity 0.83; PPV 0.94; and NPV 0.83. We fit a series of logistic regression models to assess the relationship between C2P predicted response and clinical outcome. Each model included 1 clinical prognostic factor (HR status, stage, NG, histology, HER2) as well as the C2P prediction factor. In all 5 models C2P remained a statistically significant predictor of clinical response while adjusting for the other prognostic factor. Conclusions: CDK1/2 activity is a promising novel predictive marker to predict response to taxane- containing regimens for HER2- breast cancer. We could not predict taxane sensitivity in HER2+ tumors; this finding is consistent with preclinical findings that HER2 overexpression is involved in abnormal SAC functionality. Thus, the functional SAC reflects taxane sensitivity in HER2- tumors. We are planning a large prospective study to validate these findings. No significant financial relationships to disclose.
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LoRusso, Stephen, Henry Piascik, and Karen Wonders. "Do Taxane Based Chemotherapies Impair Improvements in VO2 in Female Cancer Survivors." Medicine & Science in Sports & Exercise 51, Supplement (June 2019): 244. http://dx.doi.org/10.1249/01.mss.0000561239.26881.f0.
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Jegerski, Maura, Karen Wonders, and Stephen LoRusso. "Taxane Based Chemotherapies Impact on Balance and VO2 in Female Cancer Survivors." Medicine & Science in Sports & Exercise 51, Supplement (June 2019): 244. http://dx.doi.org/10.1249/01.mss.0000561240.21043.2e.
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McCourt, Carolyn, Sybil Dessie, Ann Marie Bradley, Joanna Schwartz, Laurent Brard, and Don S. Dizon. "Is There a Taxane-Free Interval That Predicts Response to Taxanes as a Later-Line Treatment of Recurrent Ovarian or Primary Peritoneal Cancer?" International Journal of Gynecologic Cancer 19, no. 3 (March 2009): 343–47. http://dx.doi.org/10.1111/igc.0b013e3181a12eb9.
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Objectives:Taxanes have reported response rates of 20% to 40% in recurrent ovarian cancer (ROC) but are less well studied as a later-line treatment. We reviewed our experience with taxanes in ROC to determine (1) if a taxane-free interval is associated with response rates in women with ROC and (2) if the use of intervening therapy (IT) affects subsequent response rates to taxanes.Methods:We retrospectively identified women who received first- or second-line platinum-taxane therapy and later received a single-agent taxane. Demographics, intervening regimens, and follow-up and survival data were collected. Responses were characterized by cancer antigen 125 levels based on the Gynecologic Cancer InterGroup serologic response definitions.Results:We identified 46 women who met the eligibility criteria. The median age was 57 years (range, 39-78 years). The median interval between taxanes was 25.8 months (range, 2.9-85.5 months), with 10 (21%) of the women were treated 12 months or less from their last taxane and 37 (79%) treated more than 12 months. The median number of IT was 2 (range, 0-5). Forty patients (87%) received paclitaxel; 6 (13%) received docetaxel. All patients treated 12 months or less from their last taxane responded (P = 0.02). The number of IT was associated with a better response; all women (100%) treated who had no IT, 7 (54%) of 13 women with 1 to 2 ITs, and 7 (39%) of 18 women with 3 ITs or more responded. The overall survival was 13.4 months in responders versus 10.6 months in nonresponders (P = 0.27).Conclusions:Taxanes maintain an activity as a later-line agent, even with 3 or more intervening therapies. However, the highest responses were seen if taxanes were used within 12 months of the last platinum-based combination. The lack of an increased response with aprolonged taxane-free interval is likely related to the number of IT, consistent with the emergence of multidrug resistance.
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Sathianathen, Niranjan J., Yiannis A. Philippou, Gretchen M. Kuntz, Badrinath R. Konety, Shilpa Gupta, Alastair D. Lamb, and Philipp Dahm. "Taxane-based chemohormonal therapy for metastatic hormone-sensitive prostate cancer: a Cochrane Review." BJU International 124, no. 3 (March 20, 2019): 370–72. http://dx.doi.org/10.1111/bju.14711.
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Burstein, H. J., A. Keshaviah, A. Baron, R. Hart, R. Lambert-Falls, P. K. Marcom, R. Gelman, and E. P. Winer. "Trastuzumab and vinorelbine or taxane chemotherapy for HER2+ metastatic breast cancer: The TRAVIOTA study." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 650. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.650.
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650 Background: The optimal trastuzumab/chemotherapy regimen for advanced breast cancer is not known. We performed a multicenter, randomized clinical trial to compare TRastuzumab And VInorebline Or TAxane (TRAVIOTA) chemo- and bio-therapy combination treatment given on a weekly schedule for HER2+ metastatic breast cancer. Patients and Methods: Eligible patients had stage IV breast cancer, measurable disease (by RECIST criteria), HER2+ tumors (IHC 3+ or FISH+), no prior chemotherapy or trastuzumab for advanced breast cancer, and LVEF > 50%. Patients were randomized 1:1 to trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter) with either weekly vinorelbine (25 mg/m2) or weekly taxane (paclitaxel 80 mg/m2 or docetaxel 35 mg/m2, selected by the treating investigator). The primary endpoint was response rate. The study opened in August 2001 and planned to accrue 250 patients. It was closed in December 2003 having accrued only 85 patients. Results are presented for the 81 patients who received any protocol-based therapy. Results: Patients receiving trastuzumab and vinorelbine tended to have higher response rates and TTP than those assigned trastuzumab and taxane therapy but the results were not statistically significant (see Table ). Vinorelbine therapy was associated with more frequent grade 3 or 4 hematological toxicity and dose delay because of myelosuppression. Other toxicities generally reflected the known side effects of the chemotherapy agents. Conclusions: The TRAVIOTA study suggests at least comparable clinical activity of trastuzumab with vinorelbine as with weekly taxane chemotherapy in HER2+ metastatic breast cancer, with side effect profiles consistent with previous experience with these regimens. [Table: see text] [Table: see text]
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Ali, Haythem Y., Zaid Abdel Rahman, and Jawad Sheqwara. "A differential response to cetuximab in patients with recurrent unresectable or metastatic head and neck cancer following immunotherapy (IO) exposure: An institutional experience." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e17500-e17500. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e17500.
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e17500 Background: Metastatic head and neck cancer is a diagnosis with poor prognosis and very little in terms of available active therapy. Until recently the mainstay of therapy was chemotherapy with or without cetuximab. The regimen of cetuximab (C), platinum (P) and 5FU has a response rate(RR) of 36% in the first line setting, and a PFS of 5.6 months and OS of 10.1 months. In the setting of post first line therapy immunotherapeutic agents (IO) have average RR of 15% and median OS of 8 months. Methods: We studied all patients with metastatic or recurrent head and neck cancer who were treated with an IO at our institution between May 2016 and July 2018 evaluating their entire history of therapy. 19 patient were treated with IO at our institution in the designated period of whom 9 received nivolumab (N) and 10 received pembrolizumab ( P ). Patients treated on trials were excluded. Patients who received less than 1 cycle of therapy were also excluded. 7 of the 19 patients received an IO in the first line setting after being refractory or resistant to platinum containing definitive therapy, 7 received the IO after a cetuximab (C) containing first line regimen, 1 patient received IO in second line but was naïve to C and 4 received IO in the third line setting. Results: 3 of 19 patients treated with IO had partial response, there were no complete responses, 6 patients had stable disease as their best response and 10 patients progressed at the time of their first evaluation. 11 of 19 patients received additional therapy post IO. 10 patients received taxane based therapy 5 of whom the taxane was combined with C. Of the 5 patients who received a taxane and C combination 2 had CR, 2 had PR and one had PD. Of the 5 who received other taxane regimens, 1 had PR 1 had SD and 1 had PD, 2 expired prior to their first evaluation. The patient who received a non taxane regimen all had progressive disease. Of the 4 responding patients to C regimens 1 had SD during IO therapy and 3 had PD. The longest response duration to a C regimen post IO was 628 days. Conclusions: We observe an unusual response rate among patients treated with a combination of taxanes and cetuximab after IO therapy. This finding may relate to a modifying effect of IO on sensitivity to subsequent therapy. This observation merits further investigation.
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Furlanetto, Jenny, and Sibylle Loibl. "Optimal Systemic Treatment for Early Triple-Negative Breast Cancer." Breast Care 15, no. 3 (2020): 217–26. http://dx.doi.org/10.1159/000508759.
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Background: Approximately 10–15% of all breast tumors are triple-negative breast cancer (TNBC). TNBC have a higher risk of relapse and distant metastases compared to other subtypes. The optimal systemic management of TNBC according to national and international guidelines is discussed herein. Summary: Anthracycline/taxane-based chemotherapy for patients with TNBC either in the neoadjuvant (NACT) or the adjuvant setting is considered standard of care. Exceptions are small tumors and a low-risk histology, in which chemotherapy can be spared. Dose-dense therapy is more effective in preventing recurrence and increasing survival. The use of nab-paclitaxel instead of a solvent-based taxane can lead to higher pathological complete response (pCR) rates and better outcomes. Platinum agents are effective in increasing pCR when added to anthracycline/taxane-based chemotherapy at the cost of increased toxicity. Long-term outcome data are lacking. In patients without a pCR, capecitabine leads to improved outcomes. Key Messages: The standard treatment approach of TNBC is anthracycline/taxane-based chemotherapy, preferably within the NACT setting. Dose-dense schedules as well as platinum should be considered in the NACT setting. For patients without a pCR, capecitabine is an option to improve the outcome. The role of nab-paclitaxel is under debate. In case of immunogenic tumors, checkpoint inhibitors are promising new agents that merit further investigation.
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Rogers, Jane E., and Jaffer A. Ajani. "Taxane- Versus Cisplatin-Based Chemotherapy With Radiation Therapy Is a Better Platform to Refine Esophageal Cancer Therapy." Journal of Clinical Oncology 37, no. 30 (October 20, 2019): 2805–6. http://dx.doi.org/10.1200/jco.19.01247.
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Piccart-Gebhart, Martine J., Tomasz Burzykowski, Marc Buyse, George Sledge, James Carmichael, Hans-Joachim Lück, John R. Mackey, et al. "Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer." Journal of Clinical Oncology 26, no. 12 (April 20, 2008): 1980–86. http://dx.doi.org/10.1200/jco.2007.10.8399.
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Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. Patients and Methods Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. Results Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. Conclusion Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.
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Schneider, B. P., M. Wang, V. Stearns, S. Martino, V. E. Jones, E. A. Perez, T. J. Saphner, et al. "Relationship between taxane-induced neuropathy and clinical outcomes after adjuvant chemotherapy." Journal of Clinical Oncology 29, no. 27_suppl (September 20, 2011): 270. http://dx.doi.org/10.1200/jco.2011.29.27_suppl.270.
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270 Background: Neuropathy is a common and potentially enduring and disabling complication of adjuvant taxane therapy. Recent studies have identified candidate host single nucleotide polymorphisms (SNPs) associated with taxane-induced neuropathy (Schneider et al. ASCO 2011, abstr. 1000). We therefore sought to determine whether neuropathy was associated with breast cancer recurrence. Methods: This study included 4,950 eligible women with axillary lymph node positive or high-risk node-negative breast cancer who received up to 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks x 4 (P3), (2) paclitaxel 80 mg/m2 weekly x 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks x 4 (D3), or (4) docetaxel 35 mg/m2 weekly x 12 (D1). Chemotherapy doses were based on actual body weight. Cox proportional hazards model were used to determine the relationship between neuropathy and disease free survival (DFS) and overall survival (OS) treating neuropathy status as a time dependent covariate and using a landmark analysis. Results: Of 4,702 patients who received at least 1 taxane dose, grade 2-4 neuropathy developed in 20%, 27%, 16%, and 16% in the P3, P1, D3, and D1 arms, respectively. In a model including age, tumor size, nodal status, treatment arm, neuropathy, and the neuropathy- treatment interaction, there was no relationship between neuropathy and DFS and OS in the entire population, for any of the individual treatment arms, or for any breast cancer subtypes, whether analyzed as a time-dependent covariate or using a landmark analysis. Baseline covariates associated with an increase rate of neuropathy included black race (25% vs. 19% grade 2-4, p=0.02) and obesity (21% vs. 19%, p=0.04), but not age. Conclusions: There was no association between taxane-induced neuropathy and DFS or OS in patients treated with contemporary AC-taxane therapy, including weekly paclitaxel. These findings show that taxane-induced neuropathy is not associated with outcome, thus suggesting that validation of SNPs predictive of neuropathy may be useful in identifying patients at higher risk for neuropathy but not taxane benefit and thereby improve therapeutic individualization.
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Seto, Tiffany, Navendu D. Samant, Nina Shah, Aida Shirazi, A. Dimitrios Colevas, and Jed Abraham Katzel. "Treatment patterns for patients with metastatic or recurrent head and neck cancer in a large integrated health-care system." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e18015-e18015. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e18015.
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e18015 Background: Since publication of the landmark KEYNOTE-048 Trial, pembrolizumab alone or with platinum-based chemotherapy and 5-fluorouracil (5FU) was established as a standard of care for the frontline treatment of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC), replacing the EXTREME regimen of Cetuximab with platinum and 5FU. In clinical practice, some clinicians modify the KEYNOTE-048 regimen by substituting a taxane for 5FU (i.e., Paclitaxel + Carboplatin + Pembrolizumab, PCT). Within the Kaiser Permanente Northern California (KPNCAL) network, we identified a cohort of 123 patients who received palliative first-line therapy for metastatic HNSCC to identify practice patterns in a real-world setting within a large health care delivery system. Methods: This is a data-only cohort study of all adult KPNCAL members diagnosed with metastatic HNSCC treated with palliative combination chemotherapy and/or immunotherapy between January 1, 2018 and July 31, 2020. Results: Among a cohort of 123 patients, 28 patients received the EXTREME regimen (platinum + 5FU + cetuximab), 10 received modified EXTREME (platinum + taxane + cetuximab), 14 received platinum + 5FU + pembrolizumab, 9 received platinum + taxane + pembrolizumab and 62 received single agent immunotherapy. From 2018 through mid-2020, there was an apparent shift away from cetuximab based regimens and a concurrent rise in immunotherapy-based regimens. By mid-2020, the majority of patients received an immunotherapy-based regimen (28 patients), while only 5 patients received a cetuximab based regimen (Table). Conclusions: Data from our cohort reported clinical practice patterns within a large multispecialty integrated health-care system in Northern California. Our findings highlight the marked variability in practice patterns within a single health care system for first-line metastatic therapy. While we identified trends away from cetuximab based therapy and toward immunotherapy-based therapy in clinical practice there remained wide practice variations among clinical oncologist treating patients with newly diagnosed metastatic HNSCC. This further emphasizes the need for prospective clinical trials to identify the optimal regimen or to confirm clinical equipoise between regimens among patients with metastatic or recurrent head and neck cancer. [Table: see text]
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Garon, Edward B., Giorgio Vittorio Scagliotti, Oliver Gautschi, Martin Reck, Michael Thomas, Lara Iglesias Docampo, Haralabos Kalofonos, et al. "Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy." ESMO Open 5, no. 1 (January 2020): e000567. http://dx.doi.org/10.1136/esmoopen-2019-000567.
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IntroductionNon-small-cell lung cancer (NSCLC) is a heterogeneous disease. Front-line therapy may affect responses to subsequent treatment regimens, thus influencing second-line therapy decision making. In the randomised phase 3 REVEL study, second-line ramucirumab plus docetaxel (ram+doc) versus docetaxel (doc) improved survival of patients with metastatic NSCLC. We explore efficacy, safety and quality-of-life (QoL) in REVEL based on front-line therapy.MethodsPatients were grouped by specific front-line therapy received. Overall survival (OS), progression-free survival (PFS), objective response rate, safety and QoL were assessed descriptively. Kaplan-Meier estimation and Cox proportional hazards modelling were used; frequencies reported in percentages.ResultsBaseline characteristics of 1253 patients were generally well balanced between treatment arms within each front-line therapy subgroup. For patients with non-squamous disease (n=912), induction therapies included platinum-based chemotherapy plus a taxane (n=227; 25%) or pemetrexed (n=449; 49%), with (n=172; 19%) or without bevacizumab. For patients with squamous disease (n=328), induction therapies included platinum-based chemotherapy plus gemcitabine (n=176; 54%) or a taxane (n=69; 21%). A highly selected subgroup (n=127; 14%) received pemetrexed continuation maintenance therapy. Ram+doc improved median OS and PFS versus doc across front-line therapy subgroups, as reflected by HRs ranging from 0.78 to 0.91 and 0.66 to 0.92, respectively, similar to results in the overall intention-to-treat cohort (HRs: 0.86 and 0.76, respectively). High-grade treatment-emergent adverse events of special interest (including neutropenia, febrile neutropenia, leucopenia and hypertension) were generally higher in ram+doc-treated patients relative to doc-treated patients regardless of front-line therapy. No clear differences in safety or QoL were seen across front-line therapy subgroups; outcomes were consistent with those reported in the overall intention-to-treat cohort.ConclusionsResults of this exploratory analysis suggest that second-line ram+doc may be effective regardless of prior treatment with platinum-based chemotherapy plus a taxane, pemetrexed, gemcitabine or bevacizumab. Overall, ram+doc is clinically beneficial across a wide range of patients with metastatic NSCLC who have progressed after various front-line therapies.Trial registration numberNCT01168973.
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Garces, Christopher A., and William G. Cance. "Neoadjuvant Chemotherapy of Breast Cancer." American Surgeon 70, no. 7 (July 2004): 565–69. http://dx.doi.org/10.1177/000313480407000701.
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The use of neoadjuvant chemotherapy in the treatment of breast cancer has been evolving during the past two decades. Fisher's group accomplished the scientific rationale in mouse models in the 1970s. The Milan group was the first to use neoadjuvant therapy in locally advanced breast cancer and also determined that adjuvant sequential doxorubicin with cyclophosphamide/methotrexate/fluorouracil (CMF) offered improved survival when compared to alternating CMF with doxorubicin. Other groups (M. D. Anderson and NSABP) have evaluated similar doxorubicin-based neoadjuvant therapies in locally advanced breast cancer (LABC) and in early disease. These studies have shown an increase in breast-conserving therapy (BCT) and an increase in pathologic complete response (pCR) when neoadjuvant therapy was used. Due to anthracycline resistance, taxanes were added to the doxorubicin-based neoadjuvant chemotherapy regimen with an increase in BCT and pCR than when an anthracycline regimen was used alone. Overall survival has yet to be determined when comparing an anthracycline-based regimen to the same regimen with the addition of a sequential taxane. Therefore, a combined treatment of an anthracycline/cyclophosphamide/taxane regimen is the recommended neoadjuvant chemotherapy for patients with breast cancer.
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Chou, Ching-Wen, Yu-Min Huang, Yu-Jia Chang, Chien-Yu Huang, and Chin-Sheng Hung. "Identified the novel resistant biomarkers for taxane-based therapy for triple-negative breast cancer." International Journal of Medical Sciences 18, no. 12 (2021): 2521–31. http://dx.doi.org/10.7150/ijms.59177.
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Azambuja, E., V. Durbecq, D. D. Rosa, M. Colozza, D. Larsimont, M. Piccart-Gebhart, and F. Cardoso. "HER-2 overexpression/amplification and its interaction with taxane-based therapy in breast cancer." Annals of Oncology 19, no. 2 (February 2008): 223–32. http://dx.doi.org/10.1093/annonc/mdm352.
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Pillai, Rathi N., Seth A. Brodie, Gabriel L. Sica, You Shaojin, Ge Li, Dana C. Nickleach, Liu Yuan, et al. "CHFR Protein Expression Predicts Outcomes to Taxane-Based First Line Therapy in Metastatic NSCLC." Clinical Cancer Research 19, no. 6 (February 5, 2013): 1603–11. http://dx.doi.org/10.1158/1078-0432.ccr-12-2995.
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Weiss, Anna, Sami Bashour, Limin Hsu, Kenneth R. Hess, Alastair Mark Thompson, and Nuhad K. Ibrahim. "Effect of neoadjuvant chemotherapy regimen choice in patients with breast cancer with pathologic complete response." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 570. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.570.
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570 Background: Breast cancer patients with a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize there is no difference in post-surgical recurrence free survival (RFS) between regimens used if pCR has been achieved. Methods: Breast cancer patients treated with NACT (using various regimens) between 1996 and 2011 who achieved pCR were examined, using a prospectively maintained electronic database. RFS was estimated by Kaplan-Meier method, differences between groups assessed using log-rank test. Cox proportional hazards regression analysis adjusted for age, menopausal status, stage, grade, tumor subtype, and adjuvant treatments. Results: 721 patients were identified: 40.4% Stage IIA, 21.2% IIB, 10.8% IIIA, 9.2% IIIB, 18.3% IIIC. 21.8% were hormone receptor positive (HR), 43.3% HER2 amplified, 32.7% triple negative. 50.9% of patients were treated with adriamycin-based chemotherapy plus taxane (adriamycin+taxane), 7.8% without taxane (adriamycin-taxane), 31.5% HER2 targeted therapy, and 9.8% provider choice. Median follow up was 7.4 years. There was no significant difference in RFS by treatment group (table 1). Adjusted RFS hazard ratios comparing each treatment to adriamycin+taxane were 1.25 (95% confidence interval 0.47-3.35) adriamycin-taxane, 0.90 (CI 0.37-2.20) HER2 targeted, and 1.28 (CI 0.55-2.98) provider choice. Conclusions: These data suggest that post-surgical RFS among patients with pCR is not significantly influenced by the type of NACT. Meta-analysis of randomized trial data should be explored to evaluate these findings. If RFS of pCR patients is not affected by regimen, this could allow flexibility in treatment choice and length. [Table: see text]
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Nadler, Eric S., Seongjung Joo, Jenny Black-Shinn, Marley Boyd, Joseph Zhuo, and Diana Romana Chirovsky. "Treatment patterns in recurrent/metastatic head and neck squamous cell carcinoma in the US." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 6033. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.6033.
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6033 Background: Given the most recent FDA approval of cetuximab in 2008 for treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), the objective was to assess utilization of cetuximab and other treatments for R/M HNSCC in real world setting. Methods: Adult patients (pts) with R/M HNSCC who initiated systemic therapy between 9/1/2011-12/31/2014 were identified from iKnowMedelectronic health records database (McKesson Specialty Health) supplemented with chart abstraction. Pts were followed through 12/31/2015 to collect data on clinical characteristics, treatments and survival outcomes. Results: Among 325 pts with R/M HNSCC, median age was 62 yrs; 82% were male, and 67% had oropharyngeal cancer. The most common first line (1L) regimen consisted of platinum-based combinations (76%; Table 1); 63% received platinum+taxane +/-5FU and only 8% received platinum+cetuximab +/- 5FU. Median overall survival was 13.6 months (range 11.7-16.6). Following 1L therapy, 171 pts (53%) received a 2L regimen; 57 pts (18%) received platinum monotherapy and 8% received 2L platinum+taxane +/- 5FU, while only 12% received cetuximab mono- or platinum+cetuximab + /- 5FU. Among pts receiving 1L platinum combination, 32% were re-treated with platinum based therapy of which platinum monotherapy (23%) and platinum+taxane +/- 5FU (7%) were most common. Conclusions: Despite FDA approval and NCCN guidelines recommending use of cetuximab for palliative treatment of R/M HNSCC, our study demonstrates underutilization in both 1L and 2L settings, underscoring the need to understand reasons for underutilization and the need for newer efficacious treatments. [Table: see text]
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Gandhi, S., G. G. Fletcher, A. Eisen, M. Mates, O. C. Freedman, S. F. Dent, and M. E. Trudeau. "Adjuvant chemotherapy for early female breast cancer: A systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline." Current Oncology 22 (December 18, 2014): 82. http://dx.doi.org/10.3747/co.22.2321.
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BackgroundThe Program in Evidence-Based Care (PEBC) of Cancer Care Ontario (CCO) has recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for this guideline was compiled using a systematic review to answer the question: “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” This question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (HER2) directed therapy.MethodsA systematic review was performed using the MEDLINE and EMBASE databases for the period January 2008 to May 2014. The SAGE Directory of Cancer Guidelines and websites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and was limited to randomized controlled trials (RCTs), guidelines, systematic reviews, and meta-analyses. ResultsSeveral hundred documents were retrieved that met the inclusion criteria; the Early Breast Cancer Trialists Collaborative Group (EBCTCG) meta-analyses encompassed many of the RCTs found. Several additional studies which met the inclusion criteria were included, as well as other guidelines and systematic reviews. Chemotherapy was largely reviewed as three classes of agents: anti-metabolite based regimens (e.g., CMF), anthracyclines, and taxane-based regimens. Single-agent chemotherapy in general is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline and taxane-based polychemotherapy regimens are overall considered superior to earlier generation regimens, with the most significant impact on patient survival outcomes. Various regimens with disparate anthracycline and taxane doses and schedules are options; in general, paclitaxel given every 3 weeks is inferior. Evidence does not support the use of bevacizumab in the adjuvant setting; other systemic therapy agents such as metformin and vaccines remain under investigation. Adjuvant bisphosphonates for menopausal women will be discussed in later work. ConclusionThe results of this systematic review represent a comprehensive compilation of high-level evidence which was the basis for the 2014 PEBC CCO guideline on systemic therapy for early breast cancer. The use of cytotoxic chemotherapy is presented here; the results addressing endocrine therapy and HER-2 targeted treatment, as well as the final clinical practice recommendations, are published separately in this issue.
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van den Ende, Tom, Emil ter Veer, Mélanie Machiels, Rosa Mali, Frank Abe Nijenhuis, Laura de Waal, Marety Laarman, et al. "The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis." Cancers 11, no. 1 (January 11, 2019): 80. http://dx.doi.org/10.3390/cancers11010080.
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Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38–0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58–1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28–0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.
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Markowska, J., M. Bidziáski, J. Stelmachów, E. Kraszewska, I. Ziółkowska-Seta, R. Madry, A. Timorek, A. Rembiszewska, and J. Kupryjaáczyk. "Profiles of ovarian cancer patients that benefit from taxane-platinum and platinum-based chemotherapy." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 16005. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.16005.
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16005 Background: Taxane-platinum therapy (TP; regarded as more efficient than platinum-based therapy, PC) is a standard postoperative treatment of ovarian cancer patients; however, in 20 to 30% of patients the treatment is uneffective. Normal TP53 protein is a prerequisite of cancer cell response to PC, while TP53 inefficiency may enhance tumor sensitivity to taxanes. We compared the effectiveness of PC (n=253) and TP (n=199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease. Methods: Immunohistochemical analysis with PAb1801 antibody was performed on 452 archival tumors; multivariate analysis by the Cox and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)]. The therapeutic regimens were evaluated in comparison with each other and also with interactions with clinicopathological parameters. Results: TP enhanced probability of complete remission (CR, p=.05), platinum sensitivity (PS, p=.02) and longer survival (OS, p=.008) in the TP53(+) group. In the TP53(-) group TP did not show an advantage over PC in regard to CR and PS and it diminished a chance of platinum highly sensitive response (p=.04). However, in the TP53(-) group TP appeared to diminish risk of death of patients >53 yrs (p=.063). Analysis of interactions revealed that TP therapy might be more efficient in patients with: endometrioid and clear cell carcinomas, stage III disease, G2 tumors or residual tumor > 2cm. Nevertheless, in the TP53(-) group TP did not diminish risk of death of patients =53 yrs with these characteristics. Conclusions: Our results suggest that taxane-platinum therapy should be given to patients older than 53 years and to all with TP53 accumulation in their tumors. In the group of patients =53 yrs and with TP53(-) tumors (20% of patients in our study) treatment with PC may be equally or possibly more efficient than TP. No significant financial relationships to disclose.
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Fujisawa, Yasuhiro, Yasuhiro Nakamura, Yasuhiro Kawachi, and Fujio Otsuka. "Comparison between taxane-based chemotherapy with conventional surgery-based therapy for cutaneous angiosarcoma: a single-center experience." Journal of Dermatological Treatment 25, no. 5 (June 6, 2013): 419–23. http://dx.doi.org/10.3109/09546634.2012.754839.
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Harris, Carole A., Sallie Pearson, Benjamin Daniels, Preeyaporn Srasuebkul, and Robyn L. Ward. "HER2-positive early breast cancer (HER2EBC): An Australian pattern of care study." Journal of Clinical Oncology 31, no. 31_suppl (November 1, 2013): 101. http://dx.doi.org/10.1200/jco.2013.31.31_suppl.101.
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101 Background: Clinical trials have demonstrated the benefits of trastuzumab in treating HER2EBC. However, in routine care it is unclear which patients are recommended treatment, what chemotherapy partners are used and whether patients receive all of their intended treatments. In this study we describe the real world treatment patterns in HER2EBC patients. Methods: We undertook a clinical audit of patients diagnosed with HER2EBC (stage I-III) at four Sydney-based cancer centres between 2008 and 2011. We identified patients from pathology records and extracted information on patient and cancer characteristics, treatments planned and received from medical notes and medication charts. Results: 203 patients formed the study cohort; median age 55 years (range: 21-91), all but one patient was female. 77 patients had stage I disease, 84 stage II, and 42 stage III. 176 patients (86.7%) were recommended trastuzumab-based treatment and 168 patients initiated therapy. 96 were treated with anthracycline-based chemotherapy and 70 with taxane-based chemotherapy. 76.7% completed the planned number of taxane-based treatments compared with than the 60% receiving anthracycline-based therapies; toxicity being the main reason for not completing treatment. Younger patients (OR 0.89, 95%CI 0.84-0.93, p<0.001) and those with grade 3 tumours compared to grade 1 and 2 combined (OR 3.99, 95%CI 1.31-12.08, p0.014) were more likely to be recommended trastuzumab-based treatment. Younger patients (OR 0.85, 95%CI 0.81-0.90, p <0.001) with a high HER2 gene copy number (OR 4.10, 95%CI 1.06-15.81, p 0.041) multifocal disease (OR 3.53, 95%CI 1.06- 15.82 p 0.023) and stage II and III disease (OR 0.73, 95%CI 0.25-0.90 p 0.011) were more likely to be recommended anthracycline over taxane-based therapy. Conclusions: Trastuzumab-based therapy is standard of care for patients with HER2EBC regardless of patient or cancer characteristics. Whilst chemotherapy partners are determined by patient and cancer characteristics, treatment limiting toxicities also need to be considered in order to maximise patient benefit.
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Gizzi, Marco, Giulia Baciarello, Aude Flechon, Philippe Beuzeboc, Antoine Angelergues, Guilhem Roubaud, Emmanuelle Bompas, et al. "Previous enzalutamide therapy and response to subsequent taxane therapy in metastatic castration-resistant prostate cancer." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 227. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.227.
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227 Background: Cross-resistance between taxanes and androgen receptor axis targeted agents is a matter of debate in metastatic castration-resistant prostate cancer (mCRPC). Preclinical data about response to taxanes after prior enzalutamide suggest some level of cross-resistance (van Soest et al, Eur J Cancer 2013) though this was not confirmed in other models (Al Nakouzi N, Eur Urol 2014). The first objective of this study was to assess the impact of previous enzalutamide therapy on the efficacy of subsequent taxane-based chemotherapy. The second objective was to investigate the prognosis of patients when chemotherapy was initiated in enzalutamide-pretreated patients. Methods: Data from 96 enzalutamide- and placebo-treated patients enrolled in the Prevail phase III trial were retrospectively collected from 14 centers in France. Changes in prostate specific antigen (PSA) levels, progression free survival (PFS) and RECIST criteria v 1.1 were used to determine the activity of docetaxel (n=89) or cabazitaxel (n=7) treatment. The Halabi model was used to predict survival probabilities for the enzalutamide- or placebo-pretreated patients when chemotherapy was initiated (Halabi et al, J Clin Oncol 2014). Results: Overall, 96 patients were included in this analysis (58 in the placebo arm vs. 38 in enzalutamide arm). PSA response to taxanes (defined as a decline of ≥50% from baseline) was marginally lower in enzalutamide-vs. placebo-pretreated patients (34% vs. 53%, p=0.10). PSA response in enzalutamide-pretreated patients was not different from that observed with docetaxel given every 3 weeks in TAX 327 trial (Tannock et al, NEJM 2004) (45%, p=0.20, binomial test). Median PFS and objective response rates were similar between the two groups (4.8m vs 6.7 m;p=0.14 and 45% vs 43%;p=0.83 respectively). Halabi score was well-balanced between the two groups (p=0.30). Conclusions: Taxanes retain efficacy in enzalutamide-pretreated mCRPC. At the time of first-line taxane-based chemotherapy initiation, the prognosis of enzalutamide-treated patients according to the Halabi score was not different from that of enzalutamide-naïve patients.
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Hur, Min Hee, Tae Ho Kang, Ra Joo Im, Se Won Kim, Chan Seok Yoon, Seung Sang Ko, Haekyung Lee, Ji Hyun Lee, and Sung-Soo Kang. "Clinical characteristics and chemotherapy options of triple-negative breast cancer: Role of classical CMF regimen." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 1053. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.1053.
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1053 Background: Triple-negative breast cancer is a high risk breast cancer that lacks the benefit of specific targeted therapy. We investigated the clinicopathologic characteristics between triple-negative breast cancers (TNBC) and non-TNBC. And we also analyzed the effect of chemotherapy options such as classical CMF regimen, anthracycline-based, or taxane-based chemotherapy. Methods: A total of 826 invasive breast cancer patients were evaluated from March 2003 to December 2008. We investigated them retrospectively, who had the median follow-up for 88 months. We examined the differences between TNBC compared with non-TNBC in relation to the clinicopathologic parameters, chemotherapy regimen, overall survival (OS). Results: 156 (18.9%) cases among 826 patients were triple negative breast cancers. There were significantly positive associations with younger age (below 35 years), large tumor (>2cm), high stage, poorly differentiated nuclear grade, poorly histologic grade in TNBC. Positive lymph node, lymphovascular invasion were not significantly different between TNBC and non- TNBC. A total of 677 patients were treated with chemotherapy. In TNBC patients, 142 (93.4%) patients were treated with chemotherapy more than in 535 (61.4%) of non- TNBC patients. The chemotherapy in TNBC patients was composed of classical CMF (47.9%), anthracycline-based regimen (25.4%), taxane-based regimen (26.8%). 19 cases (12%) of TNBC experienced locoregional or systemic metastases. 48 (7.2%) patients of non- TNBC did local or systemic metastases. Patients with TNBC had worse 5-year OS than with non-TNT (95.7% vs 98.6%, p=0.01). Interestingly, patients treated with CMF regimen were better 5-year OS than with anthracycline-based, or taxane-based regimen in TNBC (100% vs 96.9% vs 89.2%, p=0.001). There was no survival difference among chemotherapy regimens in non-TNBC patients. Conclusions: Patients with TNBC have poor prognosis compared with non-TNBC. Classical CMF regimen for TNBC patients may be more effective than anthracycline-based or taxane-based regimens.