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Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group

  • PHASE II STUDIES
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Summary

Purpose To evaluated the efficacy and safety of sorafenib in patients with advanced gastrointestinal stromal tumors (GIST) who failed to previous standard treatments. Experimental Design Thirty-one patients with measurable metastatic GIST who failed both imatinib and sunitinib were accrued. Sorafenib was administered orally at 400 mg twice daily until disease progression or development of intolerance. The primary endpoint was disease control rate (response + stable disease, DCR) at 24 weeks. Results Sorafenib was well tolerated, with hand-foot skin reaction, fatigue, hypertension, and abdominal pain being the most frequent adverse events. The relative dose intensity of sorafenib during the first 6 months was >80%. Four patients achieved partial response (response rate 13%, 95% CI 1–25%), and 16 (52%) had stable disease. DCR at 24 weeks was measured as 36% (95% CI 19–52%). Median progression-free and overall survivals were 4.9 and 9.7 months, respectively. Progression-free survival of patients with prior use of nilotinib (P = .0085) and with primary genotypes other than KIT exon 11 mutation (P = .0341) was significantly shorter than that of patients without. Conclusions Sorafenib showed antitumor activity in this population of imatinib and sunitinib pretreated GIST. With sorafenib, about one third of patients can maintain disease control for more than 24 weeks.

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Acknowledgements

We thank the patients who participated in this trial and the study coordinators, nurses and doctors who assisted with the research. This study was supported by a grant for GIST study from the Korean Gastric Cancer Association. Study drug (sorafenib) was kindly provided by Bayer-Schering Pharma Korea (Seoul, Korea).

Conflicts of interest

Yoon-Koo Kang received honorarium and research grant from Bayer. All other authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, South Korea

    S. H. Park

  2. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    M. H. Ryu, B. Y. Ryoo & Y. K. Kang

  3. Department of Internal Medicine, Seoul National University Hospital, Soeul, South Korea

    S. A. Im

  4. Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Hospital, Busan, South Korea

    H. C. Kwon

  5. Division of Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea

    S. S. Lee

  6. Research Institute and Hospital, National Cancer Center, Gyeonggi, South Korea

    S. R. Park

  7. Department of Oncology/Hematology, Kyungpook National University Hospital, Daegu, South Korea

    B. Y. Kang

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  1. S. H. Park
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Correspondence to Y. K. Kang.

Additional information

S. H. Park and M. H. Ryu contributed equally to the current article.

This study was registered in advance to ClinicalTrials.gov (no. NCT01091207), and presented in an abstract form at the 47th Annual Meeting of the American Society of Clinical Oncology, June 3–7, 2011, Chicago, IL.

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Park, S.H., Ryu, M.H., Ryoo, B.Y. et al. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs 30, 2377–2383 (2012). https://doi.org/10.1007/s10637-012-9795-9

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