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.
Cancer Chemother Pharmacol. 2007 Jun 27
Shimizu T, Yamamoto N, Yamada Y, Fujisaka Y, Yamada K, Fujiwara Y, Takayama K, Tokudome T, Klimovsky J, Tamura T.
Division of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo, 104-0045, Japan, ttamura@ncc.go.jp.
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/m(2) (grade 4 neutropenia for 9 days) and in two patients receiving 50 mg/m(2) (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/m(2) given over 3 h every 3 weeks. The recommended phase II dose is 40 mg/m(2), which is well tolerated and active. Data from Japanese patients are consistent with published phase I data from non-Japanese patients. |
