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01.04.2008 | Original Article

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

verfasst von: Toshio Shimizu, Noboru Yamamoto, Yasuhide Yamada, Yasuhito Fujisaka, Kazuhiko Yamada, Yutaka Fujiwara, Kyoko Takayama, Takuto Tokudome, Judith Klimovsky, Tomohide Tamura

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2008

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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.

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Titel: 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
verfasst von: Toshio Shimizu
Noboru Yamamoto
Yasuhide Yamada
Yasuhito Fujisaka
Kazuhiko Yamada
Yutaka Fujiwara
Kyoko Takayama
Takuto Tokudome
Judith Klimovsky
Tomohide Tamura
Publikationsdatum: 01.04.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2008
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-007-0530-8

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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