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1

Kreutzberger, Alfred, and Elfriede Kreutzberger. "Antineoplastika, 15. Mitt. Butylderivate der 5-Aminomethylenbarbitursäure." Archiv der Pharmazie 318, no. 9 (1985): 821–24. http://dx.doi.org/10.1002/ardp.19853180910.

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Kreutzberger, Alfred, and Michael Sellheim. "Antineoplastika XVI [1]. 4-Alkyl-6-trifluormethyl-2-ureidopyrimidine." Journal of Fluorine Chemistry 27, no. 2 (February 1985): 203–12. http://dx.doi.org/10.1016/s0022-1139(00)84989-1.

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Kreutzberger, Alfred, Peter Langner, and Jörg Stratmann. "Antineoplastika, 19. Mitt.: Darstellung vonN-[2-Chlor-4-diethylamino-(1,3,5-triazin-6-yl)]-aminosäuren." Archiv der Pharmazie 323, no. 12 (1990): 995–96. http://dx.doi.org/10.1002/ardp.19903231211.

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Kreutzberger, Alfred, Peter Langner, and Jörg Stratmann. "Antineoplastika, 17. Mitt.1): Darstellung mono- und disubstituierter 2,4-Dichlor-6-diethylamino-1,3,5-triazine." Archiv der Pharmazie 324, no. 3 (1991): 173–76. http://dx.doi.org/10.1002/ardp.19913240308.

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5

Burgaz, S., B. Karahalil, Z. Canli, F. Terzioglu, G. Ançel, R. BM Anzion, R. P. Bos, and E. Hüttner. "Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations." Human & Experimental Toxicology 21, no. 3 (March 2002): 129–35. http://dx.doi.org/10.1191/0960327102ht230oa.

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To estimate the genotoxic risk of occupational exposure to antineoplastic drugs, chromosomal aberration (CAs) frequencies in peripheral lymphocytes were determined for 20 nurses handling antineoplastics and 18 referents matched for age and sex. Urinary cyclophosphamide (CP) excretion rates, which are used as a marker for drug handling, were also measured on these nurses. We have observed significant frequencies of CAs (about 2.5-fold increase) including chromatid breaks, gaps, and acentric fragments for nurses handling antineoplastics as compared to control subjects (p<0.05, p<0.01, excluding and including gaps, respectively). The mean value of CP excretion rate for 12 nurses was 1.63 μg/24 h, suggesting that when the nurses handled CP (and other antineoplastic drugs) this particular compound was absorbed. Our study has shown that increased genetic damage was evident in nurses, at population level, due to occupational exposure to antineoplastics. Until the effects of handling antineoplastics from low-level exposure are known, it will be important to keep the exposure to a minimum.
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Kopjar, Nevenka, Davor Želježić, Vilena Kašuba, and Ružica Rozgaj. "Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers." Archives of Industrial Hygiene and Toxicology 61, no. 1 (March 1, 2010): 121–46. http://dx.doi.org/10.2478/10004-1254-61-2010-2025.

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Antineoplastični Lijekovi Kao Čimbenik Rizika u Radnom Okolišu: Mehanizmi Djelovanja na Razini Stanice i Pregled Metoda za Otkrivanje Njihovih Genotoksičnih UčinakaU članku je prikazana osnovna podjela antineoplastičnih lijekova prema mehanizmima djelovanja na razini stanice. Objašnjeni su mehanizmi genotoksičnosti najvažnijih vrsta lijekova koji se primjenjuju u okviru uobičajenih protokola za liječenje zloćudnih novotvorina. Navedena je važeća klasifikacija antineoplastika prema kancerogenom potencijalu, podaci o mutagenom potencijalu te je prikazana njihova podjela u skladu s anatomsko-terapijsko-kemijskim sustavom klasifikacije. Sustavno su prikazani najvažniji rezultati svjetskih i hrvatskih istraživanja na populacijama radnika izloženih antineoplasticima, provedenih u razdoblju 1980.-2009. s pomoću četiri najčešće primjenjivane metode: analize izmjena sestrinskih kromatida, analize kromosomskih aberacija, mikronukleus-testa i komet-testa. Objašnjena su osnovna načela navedenih metoda te raspravljene njihove prednosti i nedostaci. Biološki pokazatelji daju važne podatke o individualnoj osjetljivosti profesionalno izloženih ispitanika koji mogu poslužiti unaprjeđenju postojećih uvjeta rada i upravljanju rizicima pri izloženosti genotoksičnim agensima. Na osnovi prednosti i nedostataka citogenetičkih metoda zaključeno je da je mikronukleus-test, koji podjednako uspješno dokazuje klastogene i aneugene učinke, jedna od najboljih metoda dostupnih za otkrivanje štetnih djelovanja antineoplastičnih lijekova koji su u aktivnoj primjeni.
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Guan, Xiaodong, Haishaerjiang Wushouer, Mingchun Yang, Sheng Han, Luwen Shi, Dennis Ross-Degnan, and Anita Katharina Wagner. "Influence of government price regulation and deregulation on the price of antineoplastic medications in China: a controlled interrupted time series study." BMJ Open 9, no. 11 (November 2019): e031658. http://dx.doi.org/10.1136/bmjopen-2019-031658.

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BackgroundIn October 2012, the Chinese government established maximum retail prices for specific products, including 30 antineoplastic medications. Three years later, in June 2015, the government abolished price regulation for most medications, including all antineoplastic medications. This study examined the impacts of regulation and subsequent deregulation of prices of antineoplastic medications in China.MethodsUsing hospital procurement data and an interrupted time series with comparison series design, we examined the impacts of the policy changes on relative purchase prices (Laspeyres price index) and volumes of and spending on 52 antineoplastic medications in 699 hospitals. We identified three policy periods: prior to the initial price regulation (October 2011 to September 2012); during price regulation (October 2012 to June 2015); and after price deregulation (July 2015 to June 2016).ResultsDuring government price regulation, compared with price-unregulated cancer medications (n=22, mostly newer targeted products), the relative price of price-regulated medications (n=30, mostly chemotherapeutic products) decreased significantly (β=−0.081, p<0.001). After the government price deregulation, no significant price change occurred. Neither government price regulation nor deregulation had a significant impact on average volumes of or average spending on all antineoplastic medications immediately after the policy changes or in the longer term (p>0.05).ConclusionCompared with unregulated antineoplastics, the prices of regulated antineoplastic medications decreased after setting price caps and did not increase after deregulation. To control the rapid growth of oncology medication expenditures, more effective measures than price regulation through price caps for traditional chemotherapy are needed.
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Hong, Samuel J., Edward C. Li, Linda M. Matusiak, and Glen T. Schumock. "Spending on Antineoplastic Agents in the United States, 2011 to 2016." Journal of Oncology Practice 14, no. 11 (November 2018): e683-e691. http://dx.doi.org/10.1200/jop.18.00069.

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Purpose: Recent cancer drug approvals are lauded as being more effective with relatively fewer adverse effects, but these treatments come with a great cost to the US health care system. There is little information on recent trends in actual antineoplastic expenditures representative of the whole US health care system or by sector. Therefore, the objective of this study was to describe antineoplastic expenditures in the United States by year and sector. Methods: This was a retrospective, cross-sectional study of IQVIA (formerly QuintilesIMS) National Sales Perspective data for the period of January 1, 2011, to December 31, 2016. Actual expenditures were totaled by health care sector and calendar year, then adjusted for medical-cost inflation to 2016 dollars. Growth was calculated as the percentage increase from the previous year. Results: Total expenditures of antineoplastic agents across all channels grew from $26.8 billion in 2011 to $42.1 billion in 2016. Antineoplastic spending increased 12.2% in 2016 (compared with the previous year), followed by 15.6% in 2015, 13.4% in 2014, 6.3% in 2013, and 0.4% in 2012. Throughout the study period, 96.5% of total antineoplastic expenditures occurred within clinics, mail-order pharmacies, nonfederal hospitals, and retail pharmacies. Conclusion: Antineoplastic expenditures are expected to increase because of continuing development and approval of costly targeted cancer therapies. Cost containment and utilization management strategies must be balanced so as not to restrict access or disrupt innovation. Future policies should focus on ensuring safe and appropriate use of antineoplastics while balancing long-term drug costs.
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Olin, Jacqueline L., Olga Klibanov, Alexandre Chan, and Linda M. Spooner. "Managing Pharmacotherapy in People Living With HIV and Concomitant Malignancy." Annals of Pharmacotherapy 53, no. 8 (February 15, 2019): 812–32. http://dx.doi.org/10.1177/1060028019833038.

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Objective: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. Data Sources: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. Study Selection and Data Extraction: Article bibliographies and drug interaction databases were reviewed. Search terms included HIV, antiretroviral therapy, antineoplastic agents, malignancies, and drug interactions. Data Synthesis: In the pre–antiretroviral therapy (ART) era, malignancies in PLWH were AIDS-defining illnesses, and life expectancy was shorter. Nowadays, PLWH are living longer and developing malignancies, including lung, anal, and prostate cancers. Concurrently, the oncology landscape has evolved, with novel oral targeted agents and immunotherapies becoming routine elements of care. The increased need for and complexity with antineoplastics in PLWH has led to recommendations for multidisciplinary care of this unique population. Evaluation of DDIs requires review of metabolic pathways, absorption mechanisms, and various drug transporters associated with antineoplastics and ART. Relevance to Patient Care and Clinical Practice: This review summarizes available data of non–AIDS-defining malignancies, principles of HIV care in the patient with malignancy, and guidance for assessing DDIs between antineoplastics and ART. Summary DDI tables provide point-of-care recommendations. Conclusions: The availability of ART has transformed AIDS into a chronic medical condition, and PLWH are experiencing age-related malignancies. Pharmacists play an important role in the management of this patient population.
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S R, Vendra. "A Review on Venetoclax – An Antineoplastic Agent." Journal of Medical Science And clinical Research 05, no. 04 (April 8, 2017): 20012–15. http://dx.doi.org/10.18535/jmscr/v5i4.45.

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11

Galpin, A. J., and W. E. Evans. "Therapeutic drug monitoring in cancer management." Clinical Chemistry 39, no. 11 (November 1, 1993): 2419–30. http://dx.doi.org/10.1093/clinchem/39.11.2419.

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Abstract Several anticancer drugs display characteristics that make them suitable candidates for therapeutic drug monitoring (TDM), including substantial pharmacokinetic variability and a narrow therapeutic index. However, concentration-effect relationships (pharmacodynamics) of most antineoplastic agents have not been well defined, thus limiting the widespread clinical application of TDM for cancer chemotherapy. Strategic incorporation of pharmacokinetic studies during phase I-III clinical trials should facilitate the identification of concentration-effect relationships and the definition of clinically useful levels of treatment intensity. We review representative clinical studies that have defined pharmacodynamic relationships for methotrexate, teniposide, etoposide, carboplatin, and mercaptopurine. Given that TDM has impacted positively on the clinical use of many drugs belonging to other therapeutic classes, and that pharmacodynamic correlations have been identified in several recent studies of anticancer drugs, we consider implementation of TDM a rational strategy for optimizing the use of selected antineoplastics.
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12

Seal, Brian S., Jianying Yao, Jonathan K. Kish, Dana Stafkey-Mailey, and Michael Eaddy. "Evaluation of national treatment trends in ovarian cancer." Journal of Clinical Oncology 32, no. 30_suppl (October 20, 2014): 204. http://dx.doi.org/10.1200/jco.2014.32.30_suppl.204.

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204 Background: Evaluate patterns of care among women diagnosed with metastatic (M) and non-metastatic (NM) ovarian cancer (OvCa). Methods: Using MarketScan Commercial/Medicare databases, women ≥18 years old with primary diagnosis of OvCa continuously enrolled ≥6 months pre- and post-index diagnosis were selected. Patients receiving chemotherapy (chemo) prior to index diagnosis were excluded. Eligible patients were stratified into NM and M cohorts and M patients into those diagnosed with M ≤90 days (M1), 91-180 days (M2) and ≥ 181 days (M3) post index diagnosis. Types of treatments, time to initiation and adherence to NCCN treatment guidelines were evaluated. Results: A total of 64,483 women were included; 59,277 (91.9%) NM and 5,472 (8.1%) M. Among M patients, 70.5% were M1, 4.5% M2 and 25.0% M3. Of the NM 57.1% underwent surgery (mean = 43 days), 2.5% received chemoradiation (chemorad) therapy (mean = 618 days), 2.5% received chemo (mean = 213 (NCCN) to 496 (nonNCCN) days), 3.4% received any oral antineoplastic (chemo/non, hormone, other, mean = 635 (NCCN) to 584 (nonNCCN) days), and 1.7% received hormone therapy (mean = 537 days) post index diagnosis. In comparison 70.0% of M patients had surgery, 37.2% received chemorad, 63.9% received chemo, 10.2% received an oral antineoplastic, and 19.0% received hormone therapy. As time to M diagnosis increased, utilization of chemorad (33.5% M1 to 46.9% M3), hormone therapy (17.9% M1 to 21.6% M3), and oral antineoplastic (8.9%% M1 to 14.2% M3) increased while receipt of surgery (76.6% M1 to 53.1% M3) and chemo (68.6% M1 to 52.3% M3) decreased. Time to initiation of all treatments increased as time to M increased. Among NM patients receiving oral antineoplastic 1.9% received NCCN recommended agents compared to 66.0% of M patients (72.2% M1 to 55.7% M3).Similarly, 52.2% of NM patients receiving chemo received NCCN recommended treatment compared to 98.3% of M patients (99.0% M1 to 96.2% M3). Conclusions: As recommended by the NCCN guidelines surgery was the standard of care for all patients. Utilization of chemo, chemorad and oral antineoplastics were largely reserved for M patients. M patients with a longer duration between initial and M diagnosis were more likely to receive treatment not recommended by NCCN guidelines.
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Mertens, W. C., L. J. Cassells, D. E. Brown, V. Koertge, L. Cabana, R. Parisi, D. Naglieri-Prescod, and D. J. Higby. "Chemotherapy ordering in a computerized physician order entry (CPOE) environment: A longitudinal analysis of defects from oncologist to patient." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 6040. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.6040.

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6040 Background: While published data suggest low chemotherapy error rates, the rate of chemotherapy ordering process defects and who detects them remains uncertain. Methods: Outpatient treatment plans/orders were prospectively evaluated by pharmacy prior to preparation, then by nursing prior to administration. Data collected included the nature of defects, how detected, utility of regimen-specific care sets (facilitating antineoplastic dose calculation and adjunct agent selection), and patient impact. Results: Pharmacy recognized problems with 36% of orders (comprising 1,082 cycles/4,600 drugs), with 34% incomplete (absent orders 17%; missing cycle number 12.5%; other items 4%). Pharmacy identified incorrect orders in 6% (dose calculation 2%; cycle number 1.5%; other items 2.5%). Incomplete orders were more likely to have incorrect items (11.6% v. 3.5% if complete, p < .001). Care set use (76% of cycles) was associated with fewer overall problems and incomplete orders (both p < .001), with reduced absent orders and missing antiemetics, but not antineoplastics. Care set orders exhibited a trend for fewer incorrect items (p=.06). Nursing recognized problems with 14.6% of orders, again most commonly incomplete orders (10%; absent orders 7%; missing antiemetic or antineoplastic drug 4.6%); fewer missing items resulted from care set use (p < .001). Nursing detected fewer orders with problems and missing items but more instances of missing antineoplastic and antiemetic agents (all p < .001) despite prior pharmacy review. Nursing identified incorrect orders in 5% (wrong dosage 3.4%; wrong drug 2.5%) and classified 4% of cycles as having an error (“near miss” 3.3%; more serious error reaching the patient 0.6%). Conclusions: Defects in chemotherapy orders are common despite the relatively low error rate. The predominant defects–incomplete orders–are associated with incorrect items. Both care sets and pharmacy review reduce but do not eliminate incomplete orders; the effect on incorrect orders is smaller. Even with CPOE, sequential pharmacy and nursing review remain critical to reducing order defects; additional software enhancements are needed to further reduce defects. No significant financial relationships to disclose.
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Das, Swagatika, H. Inci Gul, Umashankar Das, Jan Balzarini, Stephen G. Dimmock, and Jonathan R. Dimmock. "Novel Conjugated Unsaturated Ketones with Submicromolar Potencies Towards some Leukemic and Colon Cancer Cells." Medicinal Chemistry 15, no. 4 (May 20, 2019): 430–38. http://dx.doi.org/10.2174/1573406414666181015142633.

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Background: Cancer continues to be the major health burden worldwide. There is an urgent need for the development of novel antineoplastic compounds to treat this devastating condition. Various alkylating anticancer drugs have been employed in the clinic for treating cancers. Unsaturated conjugated ketones are a group of alkylators which are of significant interest as potent antineoplastic agents. Objective: The goal of this study is to discover unsaturated conjugated ketones which are novel potent cytotoxins displaying growth-inhibitory properties towards neoplasms and also to serve as cytotoxic warheads in drug development. Methods: A variety of 3,5-bis (benzylidene)-4-piperidones 2a-n were synthesized and evaluated against a number of neoplastic cell lines. The short-term neurotoxicity of 2a-k, n was evaluated in mice by i.p. administration using doses level of 30, 100 and 300 mg/kg. Statistical correlations for determining structure-activity relationships were performed using an SPSS software. Results: A number of compounds display cytotoxic potencies in the region of 10-7 to 10-8 M and some of the structural features contributing to the cytotoxicity were identified. Compounds 2a-d, 2h demonstrated substantially higher cytotoxic potencies compared to melphalan and 5- fluorouracil against a panel of leukemic and colon cancer cell lines. These lead cytotoxins comply with drug-likeness properties. In general, the antineoplastics 2 are well tolerated in mice using a short-term neurotoxicity screening. Conclusion: In general, this group of compounds comprises excellent cytotoxic agents, which warrant their further development as cytotoxic warheads.
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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1197 (April 2008): 7. http://dx.doi.org/10.2165/00128415-200811970-00020.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1197 (April 2008): 7–8. http://dx.doi.org/10.2165/00128415-200811970-00022.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1197 (April 2008): 8. http://dx.doi.org/10.2165/00128415-200811970-00025.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1198 (April 2008): 6. http://dx.doi.org/10.2165/00128415-200811980-00017.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1199 (April 2008): 8. http://dx.doi.org/10.2165/00128415-200811990-00018.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1201 (May 2008): 8. http://dx.doi.org/10.2165/00128415-200812010-00020.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1202 (May 2008): 6–7. http://dx.doi.org/10.2165/00128415-200812020-00015.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1203 (May 2008): 8–9. http://dx.doi.org/10.2165/00128415-200812030-00022.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1203 (May 2008): 8. http://dx.doi.org/10.2165/00128415-200812030-00023.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1207 (June 2008): 8–9. http://dx.doi.org/10.2165/00128415-200812070-00021.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1208 (June 2008): 7. http://dx.doi.org/10.2165/00128415-200812080-00022.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1209 (July 2008): 8–9. http://dx.doi.org/10.2165/00128415-200812090-00025.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1209 (July 2008): 8. http://dx.doi.org/10.2165/00128415-200812090-00027.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1209 (July 2008): 9. http://dx.doi.org/10.2165/00128415-200812090-00030.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1210 (July 2008): 7–8. http://dx.doi.org/10.2165/00128415-200812100-00019.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1211 (July 2008): 7–8. http://dx.doi.org/10.2165/00128415-200812110-00020.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1212 (July 2008): 8. http://dx.doi.org/10.2165/00128415-200812120-00024.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1213 (August 2008): 8. http://dx.doi.org/10.2165/00128415-200812130-00019.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1216 (August 2008): 8. http://dx.doi.org/10.2165/00128415-200812160-00019.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1218 (September 2008): 7. http://dx.doi.org/10.2165/00128415-200812180-00018.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1219 (September 2008): 7. http://dx.doi.org/10.2165/00128415-200812190-00018.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1222 (October 2008): 7. http://dx.doi.org/10.2165/00128415-200812220-00019.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1223 (October 2008): 4–5. http://dx.doi.org/10.2165/00128415-200812230-00012.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1225 (October 2008): 6. http://dx.doi.org/10.2165/00128415-200812250-00016.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1228 (November 2008): 7. http://dx.doi.org/10.2165/00128415-200812280-00020.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1228 (November 2008): 7–8. http://dx.doi.org/10.2165/00128415-200812280-00021.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1320 (September 2010): 11. http://dx.doi.org/10.2165/00128415-201013200-00032.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1320 (September 2010): 12. http://dx.doi.org/10.2165/00128415-201013200-00035.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1323 (October 2010): 9. http://dx.doi.org/10.2165/00128415-201013230-00024.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1324 (October 2010): 11–12. http://dx.doi.org/10.2165/00128415-201013240-00026.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1325 (October 2010): 8. http://dx.doi.org/10.2165/00128415-201013250-00022.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1325 (October 2010): 8. http://dx.doi.org/10.2165/00128415-201013250-00023.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1328 (November 2010): 8. http://dx.doi.org/10.2165/00128415-201013280-00023.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1282 (December 2009): 10. http://dx.doi.org/10.2165/00128415-200912820-00032.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1282 (December 2009): 10. http://dx.doi.org/10.2165/00128415-200912820-00035.

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&NA;. "Antineoplastics." Reactions Weekly &NA;, no. 1283 (January 2010): 13. http://dx.doi.org/10.2165/00128415-201012830-00042.

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