A phase II trial of S-1 and oxaliplatin in patients with advanced hepatocellular carcinoma

Background: Oxaliplatin is a platinum derivative that has shown efficacy in advanced hepatocellular carcinoma. S-1 is an oral fluoropyrimidine that has substituted for 5-fluorouracil in many cancers. This was a multicenter, openlabel, single-arm phase II trial that evaluated the efficacy of S-1 and oxaliplatin (SOX) in advanced hepatocellular carcinoma. All patients included in the present study were systemic treatment-naive. Prior treatment with sorafenib was allowed, but other treatments were not. Methods: Patients received S-1 (40 mg/m(2) twice daily from day 1-14) and oxaliplatin (130 mg/m(2) on day 1) every 3 weeks. The primary end point was time to progression (TTP). Secondary end points included progression-free survival, overall survival (OS), response rate, and safety profile. Results: Thirty six patients with advanced hepatocellular carcinoma were included in this study. The median TTP was 3. 0 months (95% confidence interval (CI), 0.75-5.25), and the median OS was 10.3 months (95% CI, 6.4-14.3). Bone metastasis was associated with poorer TTP and OS. The efficacy of SOX was unaffected by prior sorafenib or locoregional therapy. The objective response rate was 13.9%. No grade 4 toxicity or death from adverse events occurred. The most common grade 3 toxicities were neutropenia (13.9%), thrombocytopenia (13.9%), and diarrhea (8.3%). Conclusions: Although this trial did not meet its primary end point, the SOX regimen showed comparable efficacy and safety to the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen. As the SOX regimen is easier for patients, SOX may be a reasonable substitute for FOLFOX in hepatocellular carcinoma.