Ixabepilone: A new antimitotic for the treatment of metastatic breast cancer

作者：Bhushan Shriya; Walko Christine M^*

来源：Annals of Pharmacotherapy, 2008, 42(9): 1252-1261.

DOI：10.1345/aph.1L058

• BMS-247550
• breast cancer
• epothilones
• ixabepilone

OBJECTIVE: To evaluate the safety and efficacy of ixabepilone as a new antimitotic chemotherapeutic agent for the treatment of breast cancer.
DATA SOURCES: Data were identified by searches of MEDLINE, PubMed, and American Society of Clinical Oncology abstracts from 1966 to March 2008, using the primary search terms ixabepilone, epothilones, BMS-247550, and breast cancer.
STUDY SELECTION AND DATA EXTRACTION: Phase 1, Phase 2, and Phase 3 clinical trials examining the safety and efficacy of ixabepilone and its place in cancer treatment were reviewed. Preference was given to large Phase 2 and 3 clinical trials in the breast cancer population. Manufacturer product information was used to supplement data lacking in published trials.
DATA SYNTHESIS: Ixabepilone belongs to a novel class of drugs, the epothilones, which are nontaxane microtubule-stabilizing agents. Ixabepilone, in combination with capecitabine, has been approved by the Food and Drug Administration for treatment in patients with metastatic or locally advanced breast cancer that progresses after anthracycline and taxane therapy, or in patients with taxane-resistant cancer with contraindication to further anthracycline therapy. Ixabepilone has also been approved as monotherapy in patients with metastatic and locally advanced breast cancer refractory to taxanes, anthracyclines, and capecitabine. The most common adverse reactions reported by 20% or more of the patients receiving ixabepilone were peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. The most common hematologic abnormalities seen in more than 40% of the patients include neutropenia, leukopenia, anemia, and thrombocytopenia. Premedication with histamine H-1 and H-2 antagonists is recommended to prevent hypersensitivity reactions.
CONCLUSIONS: Based on the clinical trials reviewed here and the current information available, ixabepilone is a welcome addition to the options available for the treatment of patients with metastatic breast cancer refractory to standard therapy.

• 出版日期2008-9