Pharmacy & Therapeutics - September 2008 - (Page 529)

DRUG FORECAST tion to the armamentarium of therapeutic agents available for patients with metastatic breast cancer when resistance to active agents has developed through earlier lines of therapy. For this purpose, ixabepilone has shown clinical benefits for patients across a wide spectrum of this disease, including those with extensive, aggressive, and heavily pretreated tumors. It has also demonstrated synergistic activity when given with cap ecitabine, an antineoplastic agent that is commonly used for refractory disease. On the basis of positive phase 2 and 3 clinical trial data, ixabepilone has now received regulatory approval for use with capecitabine for patients with metastatic or locally advanced breast cancer after failure of an anthracycline and a taxane and as monotherapy in the event of failure with an anthracycline, a taxane, and capecitabine. In phase 2 studies, ixabepilone alone has demonstrated encouraging activity against advanced and metastatic disease across several therapy lines, suggesting that it may have the potential to replace taxanes as initial therapy in selected patients in the metastatic setting and may warrant investigation as an adjuvant therapy for early breast cancer.65 The efficacy of ixabepilone may be enhanced through its use in combination with other antineoplastic agents; several studies in which ixabepilone is combined with targeted therapies are ongoing or planned.66 Most notably, a phase 2 randomized trial (NCT00370552) is now under way to compare two schedules of Table 4 Treatment-Related Adverse Events (%) Occurring in 10% of More of Patients in Clinical Trials Of Ixabepilone Monotherapy in Metastatic Breast Cancer: Key Phase 2 Trials Denduluri et al.40 (n = 23) 52 (Grade 3/4: 0) 78 (Grade 3/4: 13) 30 87 61 – 39 48 – – – 56 56 – – – – – – 0 9 65 Roché et al.39 (n = 65) 71 (Grade 3/4: 20) 68 (Grade 3/4: 6) 97 92 54 32 26 29 22 – 18 20 17 14 8 14 12 14 14 6 6 11 Low et al.38 (n = 37) 54 (Grade 3/4: 3) 64 (Grade 3/4: 13) 52 54 54 – 21 35 – – – 27 30 – – – – – – 14 – 33 Thomas et al.37 (n = 49) 63 (Grade 3/4: 12) 76 (Grade 3/4: 27) 84 43 57 28 41 31 12 – 18 20 8 16 10 – 8 65 12 6 – – Perez et al.36 (n = 126) 60 (Grade 3/4: 14) 50 (Grade 3/4: 14) 49 48 42 29 29 22 – 20 19 16 9 – 13 11 – 8 – – 10 6 Adverse Event Nonhematological toxicity Peripheral sensory neuropathy Fatigue/asthenia Myalgia, arthralgia Alopecia Nausea Stomatitis, mucositis, pharyngitis Vomiting Diarrhea Rash Musculoskeletal pain Anorexia Constipation Nail changes Fever Abdominal pain, cramping Headache Neuropathic pain Pain, other Infection without neutropenia Infection, febrile neutropenia Motor neuropathy Taste disturbance, dysgeusia Hematological toxicity Neutropenia Leukopenia Anemia Thrombocytopenia 87 (Grade 3/4: 22) – 83 (Grade 3/4: 0) 52 (Grade 3/4: 4) 89 (Grade 3/4: 58) 92 (Grade 3/4: 50) 92 (Grade 3/4: 3) 40 (Grade 3/ 4: 0) 67 (Grade 3/4: 35) – 73 (Grade 3/4: ) 40 (Grade 3/4: 8) – (Grade 3/4: 53) 6 (Grade 3/4: 2) 6 (Grade 3/4: 4) – 79 (Grade 3/4: 54) 90 (Grade 3/4: 49) 84 (Grade 3/4: 8) 44 (Grade 3/4: 8) * Two trials are omitted, because minimal adverse event data were reported in one trial41 and patient numbers were low in the other.42 Grade 3/4 = National Cancer Institute Common Toxicity Criteria (CTC) grade 3 or 4. Vol. 33 No. 9 • September 2008 • P&T® 529

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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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