Pharmacy & Therapeutics - September 2008 - (Page 530)

DRUG FORECAST ixabepilone plus bevacizumab (Avastin, Genentech), with paclitaxel plus bevacizumab given as a first-line therapy for locally recurrent or metastatic breast cancer.66 Ixabepilone has a manageable safety profile. The prescribing information contains four warnings and precautions, including those regarding hypersensitivity (typically related to the diluent; treated with premedication with histamine antagonists) and fetal harm when administered to pregnant women. Additional warnings relate to neuropathy (primarily sensory) and myelosuppression. Neuropathy is cumulative, is generally reversible, and can be managed by dose adjustment and treatment delays. Myelosuppression (typically neutropenia) can be managed with dose adjustments.18 Ixabepilone represents a promising addition to the therapeutic options available for advanced breast cancer. Overall survival data from phase 3 clinical trials are expected to be available in the near future. Through an extensive clinical development program, ixabepilone has demonstrated antitumor activity for a wide range of solid tumors. 2005;205:275–292. 10. Lee JJ, Swain SM. Development of novel chemotherapeutic agents to evade the mechanisms of multidrug resistance (MDR). Semin Oncol 2005;32(Suppl 7):S22–S26. 11. Clarke R, Leonessa F, Trock B. Multidrug resistance/P-glycoprotein and breast cancer: Review and meta-analysis. Semin Oncol 2005;32(Suppl 7):S9–S15. 12. Fornier M. Epothilones in breast cancer: Review of clinical experience. Ann Oncol 2007;18(Suppl 5):S16–S21. 13. Fojo AT, Menefee M. Microtubule targeting agents: Basic mechanisms of multidrug resistance (MDR). Semin Oncol 2005;32(Suppl 7):S3–S8. 14. Faneyte IF, Kristel PM, van de Vijver MJ. Multidrug resistance associated genes MRP1, MRP2 and MRP3 in primary and anthracycline exposed breast cancer. Anticancer Res 2004;24:2931–2939. 15. Burger H, Foekens JA, Look MP, et al. RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: Correlation with chemotherapeutic response. Clin Cancer Res 2003;9:827–836. 16. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2positive advanced breast cancer. N Engl J Med 2006;355:2733–2743. 17. Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of cap ecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005;23:792–799. 18. Ixempra (ixabepilone), package insert. Princeton, NJ: Bristol-Myers Squibb; October 2007. 19. Pivot X, Dufresne A, Villanueva C. Efficacy and safety of ixabepilone, a novel epothilone analogue. Clin Breast Cancer 2007;7:543–549. 20. Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class of microtubulestabilizing agents with a taxol-like mechanism of action. Cancer Res 1995;55: 2325–2333. 21. Cortes J, Baselga J. Targeting the microtubules in breast cancer beyond taxanes: The epothilones. Oncologist 2007;12:271– 280. 22. Nettles JH, Li H, Cornett B, Krahn JM, Snyder JP, Downing KH. The binding mode of epothilone A on α,β-tubulin by electron crystallography. Science 2004; 305:866–869. 23. Lee FY, Borzilleri R, Fairchild CR, et al. BMS-247550: A novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res 2001;7:1429–1437. 24. Bode CJ, Gupta ML Jr, Reiff EA, et al. Epothilone and paclitaxel: Unexpected differences in promoting the assembly and stabilization of yeast microtubules. Biochemistry 2002;41:3870–3874. 25. Brooks TA, Minderman H, O’Loughlin KL, et al. Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Mol Cancer Ther 2003;2:1195–1205. Rowinsky EK, Calvo E. Novel agents that target tublin and related elements. Semin Oncol 2006;33:421–435. Goodin S, Kane MP, Rubin EH. Epo thilones: Mechanism of action and biologic activity. J Clin Oncol 2004;22:2015– 2025. Abraham J, Agrawal M, Bakke S, et al. Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days. J Clin Oncol 2003; 21:1866–1873. Mani S, McDaid H, Hamilton A, et al. Phase I clinical and pharmacokinetic study of BMS-247550, a novel derivative of epothilone B, in solid tumors. Clin Cancer Res 2004;10:1289–1298. Spriggs DR, Soignet S, Bievenu B, et al. Phase 1 first-in-man study of epothilone B analog BMS-247550 in patients with advanced cancer (American Society of Clinical Oncology meeting, Abstract 428a). Proc Am Soc Clin Oncol 2001;20. Gadgeel SM, Wozniak A, Boinpally RR, et al. Phase I clinical trial of BMS-247550, a derivative of epothilone B, using accelerated titration 2B design. Clin Cancer Res 2005;11:6233–6239. Zhuang SH, Agrawal M, Edgerly M, et al. A phase I clinical trial of ixabepilone (BMS-247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days. Cancer 2005;103: 1932–1938. Awada A, Bleiberg H, de Valeriola D, et al. Phase I clinical and pharmacology study of the epothilone analog BMS247550 given weekly in patients with advanced solid tumors (American Society of Clinical Oncology meeting, Abstract 427). Proc Am Soc Clin Oncol 2001;20. Hao D, Hammond LA, deBono JS, et al. Continuous weekly administration of the epothilone-B derivative, BMS-247550 (NSC710428): A phase I and pharmacokinetic (PK) study (American Society of Clinical Oncology meeting, Abstract 411). Proc Am Soc Clin Oncol 2002;21. Burris HA, Awada A, Jones S, et al. Phase I study of the novel epothilone BMS247550 administered weekly in patients with advanced malignancies (American Society of Clinical Oncology meeting, Abstract 412). Proc Am Soc Clin Oncol 2002; 21. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol 2007;25:3407–3414. Thomas E, Tabernero J, Fornier M, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol 2007;25:3399– 3406. Low JA, Wedam SB, Lee JJ, et al. Phase 26. 27. 28. 29. 30. 31. 32. REFERENCES 1. 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Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

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