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Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate

  • PHASE II STUDIES
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Summary

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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Acknowledgements

The authors thank Atsushi Sato (Showa University Toyosu Hospital) and Yoshitaka Inaba (Aichi Cancer Center) for independent radiologic review, Nozomu Fuse (National Cancer Center Hospital East) and Yasuhiro Shimada (National Cancer Center Hospital) for their contributions as co-investigators, and Charles Baum (Pfizer Inc.) for his help in designing the study. This study was sponsored by Pfizer Inc. Medical writing services and editorial assistance were provided by ACUMED® (Tytherington, UK), with funding from Pfizer Inc.

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Author notes

  1. Kuniaki Shirao

    Present address: Department of Medical Oncology, Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

  2. Kei Muro

    Present address: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

Authors and Affiliations

  1. Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Kuniaki Shirao

  2. Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Toshirou Nishida

  3. Division of Digestive Endoscopy/Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Toshihiko Doi & Atsushi Ohtsu

  4. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan

    Yoshito Komatsu

  5. Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Kei Muro

  6. Pfizer Japan Inc., Tokyo, Japan

    Yinhua Li & Eiji Ueda

Authors
  1. Kuniaki Shirao
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Correspondence to Kuniaki Shirao.

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Shirao, K., Nishida, T., Doi, T. et al. Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate. Invest New Drugs 28, 866–875 (2010). https://doi.org/10.1007/s10637-009-9306-9

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  • DOI: https://doi.org/10.1007/s10637-009-9306-9

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