TY - JOUR
T1 - Phase 1 trial of S-1 in combination with sorafenib for patients with advanced hepatocellular carcinoma
AU - Lee, Su Jin
AU - Lee, Jeeyun
AU - Park, Se Hoon
AU - Park, Joon Oh
AU - Park, Young Suk
AU - Kang, Won Ki
AU - Lee, Jongtae
AU - Yim, Dong Seok
AU - Lim, Ho Yeong
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Hepatocellular carcinoma
KW - Phase 1 trial
KW - S-1
KW - Sorafenib
UR - http://www.scopus.com/inward/record.url?scp=84866734676&partnerID=8YFLogxK
U2 - 10.1007/s10637-011-9706-5
DO - 10.1007/s10637-011-9706-5
M3 - Article
C2 - 21695438
AN - SCOPUS:84866734676
SN - 0167-6997
VL - 30
SP - 1540
EP - 1547
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 4
ER -