| Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate. | |
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MedLine Citation:
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PMID: 19730791 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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PURPOSE: To establish a recommended sunitinib dosing schedule in Japanese patients with imatinib-resistant/intolerant gastrointestinal stromal tumor (GIST) and to evaluate the efficacy, safety/tolerability, pharmacokinetics, and pharmacodynamics of sunitinib using this schedule. PATIENTS AND METHODS: In the phase I part of this open-label phase I/II trial, Japanese GIST patients received 25, 50, or 75 mg/day of sunitinib on Schedule 4/2 (4 weeks on treatment; 2 weeks off treatment) following imatinib failure. In phase II, patients received the recommended (maximum tolerated) dose on this schedule; the primary endpoint was clinical benefit rate (CBR; percent objective responses or stable disease [SD] ≥22 weeks). Additional efficacy, safety, pharmacokinetic, and biomarker analyses were performed. RESULTS: In phase I (12 patients), the recommended dose was determined to be 50 mg/day. Sunitinib pharmacokinetics were similar to those observed in studies with Western patients. In the phase II part (36 patients), the CBR was 39% (95% CI: 23–57%; 11% partial responses, 28% SD ≥22 weeks). The most common treatment-related non-hematologic adverse events (AEs) were hand–foot syndrome (86%) and fatigue (67%). A trend towards a correlation between decreases from baseline in plasma soluble KIT levels and improved CB was found. CONCLUSIONS: The pharmacokinetics observed and clinical outcomes achieved in Japanese GIST patients on sunitinib (50 mg/day, Schedule 4/2) after imatinib failure appeared similar to those of Western patients in previous sunitinib trials. Although some serious AEs were observed, AEs were generally manageable using dose interruption/modification and/or standard medical treatments. |
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Authors:
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Kuniaki Shirao; Toshirou Nishida; Toshihiko Doi; Yoshito Komatsu; Kei Muro; Yinhua Li; Eiji Ueda; Atsushi Ohtsu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Investigational new drugs Volume: 28 ISSN: 1573-0646 ISO Abbreviation: Invest New Drugs Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309330 Medline TA: Invest New Drugs Country: United States |
Other Details:
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Languages: eng Pagination: 866-75 Citation Subset: IM |
Affiliation:
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Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. kshirao@med.oita-u.ac.jp |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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