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Cancer Chemother Pharmacol. 2008 Apr;61(5):751-8. Epub 2007 Jun 27.

Phase I clinical and pharmacokinetic study of 3-weekly, 3-h infusion of ixabepilone (BMS-247550), an epothilone B analog, in Japanese patients with refractory solid tumors.

Author information

1
Division of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan. tshimizu@nara.med.kindai.ac.jp

Abstract

BACKGROUND:

Ixabepilone (BMS-247550) is the first in a new class of anti-neoplastic agents, the epothilone analogs, and is a highly active non-taxane anti-microtubule agent. This phase I study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety profile, pharmacokinetics, and antitumor activity of ixabepilone in Japanese patients.

PATIENTS AND METHODS:

Patients with solid tumors previously treated with up to four chemotherapy regimens received a 3-h intravenous infusion of ixabepilone every 3 weeks.

RESULTS:

Fourteen patients received 43 cycles (median 3, range 1-8). The most common adverse events were neutropenia, mild-to-moderate fatigue, anemia, and peripheral neuropathy. DLTs occurred in one patient receiving 40 mg/m2 (grade 4 neutropenia for 9 days) and in two patients receiving 50 mg/m2 (grade 3 mucositis, ileus and febrile neutropenia; grade 4 neutropenia for 10 days). One paclitaxel- and docetaxel-pretreated patient with non-small cell lung cancer achieved a partial response lasting for 3 months; six additional patients (43%) achieved disease stabilization with tumor shrinkage of 3-35%. The plasma concentration-time profiles of ixabepilone during cycle 1 were similar across all doses evaluated.

CONCLUSIONS:

The MTD of ixabepilone is 50 mg/m2 given over 3 h every 3 weeks. The recommended phase II dose is 40 mg/m2, which is well tolerated and active. Data from Japanese patients are consistent with published phase I data from non-Japanese patients.

PMID:
17594093
DOI:
10.1007/s00280-007-0530-8
[Indexed for MEDLINE]

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