title: Phase 1 trial of S-1 in combination with sorafenib for patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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/m(2)/day + D1-21 sorafenib 400 mg bid; level 2, D1-14 S-1 60 mg/m(2)/day + D1-21 sorafenib 400 mg bid; level 3,, D1-14 S-1 70 mg/m(2)/day + D1-21 sorafenib 400 mg bid; level 4, D1-14 S-1 80 mg/m(2)/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.
  
  
  CONCLUSIONS
  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/m(2) twice daily, respectively.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.forename: Jongtae
authors.initials: J
authors.lastname: Lee
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Yim
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010094:Oxonic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077157:Sorafenib; D005641:Tegafur / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D004338:Drug Combinations; D010671:Phenylurea Compounds; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D009536:Niacinamide; D010094:Oxonic Acid; D000077157:Sorafenib; D005472:Fluorouracil