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Investigational New Drugs

, Volume 30, Issue 1, pp 306–315 | Cite as

Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a first-line treatment in patients with advanced gastric cancer

  • Chul Kim
  • Jae-Lyun Lee
  • Yoon Hee Choi
  • Byung Woog Kang
  • Min-Hee Ryu
  • Heung Moon Chang
  • Tae Won Kim
  • Yoon-Koo Kang
PHASE I STUDIES

Summary

Background To define maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary efficacy of sorafenib plus capecitabine/cisplatin in advanced gastric cancer (AGC) patients. Methods Four dose-level combinations were tested in a standard 3 + 3 dose escalation design. Level 1: sorafenib 400 mg/d, capecitabine 1,600 mg/m2/d, cisplatin 80 mg/m2. Level 2: sorafenib 800 mg/d, capecitabine 1,600 mg/m2/d, cisplatin 80 mg/m2. Level 3: sorafenib 800 mg/d, capecitabine 2,000 mg/m2/d, cisplatin 80 mg/m2. Level 1A: sorafenib 800 mg/d, capecitabine 1,600 mg/m2/d, cisplatin 60 mg/m2. Results There were 1 DLT at Level 2, and 2 DLTs at Level 3 (Level 3 was MTD). Since the relative dose intensity (RDI) of sorafenib and capecitabine could not be maintained at Level 2, Level 1A was newly investigated. As no DLT was observed and RDI remained above 80%, Level 1A is the recommended dose for the next clinical trial. Objective response rate was 62.5% (10 of 16 patients, 95% CI; 38.8–86.2%). Median progression-free survival and overall survival were 10.0 months (95% CI; 7.4–13.8) and 14.7 months (95% CI; 12.0–20.0), respectively. Conclusions Sorafenib 400 mg bid daily, capecitabine 800 mg/m2 bid (days 1–14), and cisplatin 60 mg/m2 (day 1) is recommended for further development in AGC.

Keywords

Sorafenib Gastric cancer Phase I study Capecitabine Cisplatin 

Notes

Acknowledgement

This work was supported by the donation of study drug (sorafenib) from Bayer Schering Pharma AG. Part of this work was presented as a poster at the 45th ASCO annual meeting in Orlando, Florida, USA and the ECCO 15 and 34th ESMO multidisciplinary congress in Berlin, Germany, 2009.

Financial disclosure

Dr Yoon-Koo Kang received honoraria for lecture and advisory board from Bayer Schering Pharma AG and Roche. Besides, there is no conflict of interest to be reported from other authors.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Chul Kim
    • 1
  • Jae-Lyun Lee
    • 1
  • Yoon Hee Choi
    • 1
  • Byung Woog Kang
    • 1
  • Min-Hee Ryu
    • 1
  • Heung Moon Chang
    • 1
  • Tae Won Kim
    • 1
  • Yoon-Koo Kang
    • 1
  1. 1.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea

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