Phase 1 trial of S-1 in combination with sorafenib for patients with advanced hepatocellular carcinoma

Su Jin Lee, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Won Ki Kang, Jongtae Lee, Dong Seok Yim, Ho Yeong Lim

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15 Scopus citations

Abstract

Purpose Sorafenib is a multi-kinase inhibitor, which was approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). We conducted a phase 1 study of sorafenib plus S-1 in patients with advanced HCC. Experimental design We designed to escalate S-1 at 4 different dose levels with fixed dose of sorafenib. Four dose levels were as follows: level 1, D1-14 S-1 50 mg/m2/day + D1-21 sorafenib 400 mg bid; level 2, D1-14 S-1 60 mg/m2/ day + D1-21 sorafenib 400 mg bid; level 3, D1-14 S-1 70 mg/m2/day + D1-21 sorafenib 400 mg bid; level 4, D1-14 S-1 80 mg/m2/day + D1-21 sorafenib 400 mg bid. The treatment was repeated every 3 weeks. Results: From August 2009 to July 2010, 20 patients with advanced HCC were enrolled. The median age was 48 years (range, 29-74). Eighteen (90%) patients had hepatitis B viral infection and 19 (95%) patients were rated as Child-Pugh class A. The dose-limiting toxicities were grade 4 infection and thrombocytopenia. After a median follow-up duration of 8.6 months (range, 3.7-14.2 months), median PFS was 3.9 months (95% CI, 0.8-7.0 months) and median OS was 10.4 months (95% CI, 0-22.4 months). In pharmacokinetic analysis, there was no statistically significant drug interaction between sorafenib and S-1. Conclusion:s The combination of sorafenib and S-1 showed tolerable toxicity profile and modest clinical efficacy in patients with advanced HCC. The recommended dose of sorafenib and S-1 was 400 mg twice daily and 40 mg/m2 twice daily, respectively.

Original languageEnglish
Pages (from-to)1540-1547
Number of pages8
JournalInvestigational New Drugs
Volume30
Issue number4
DOIs
StatePublished - Aug 2012

Keywords

  • Hepatocellular carcinoma
  • Phase 1 trial
  • S-1
  • Sorafenib

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