A phase II study of 5-fluorouracil and cisplatin systemic chemotherapy for inoperable hepatocellular carcinoma with α fetoprotein as a predictive and prognostic marker

The objective of this study was to evaluate the efficacy and toxicity of 5-fluorouracil and cisplatin in patients with inoperable hepatocellular carcinoma (HCC), and to evaluate the utility of α fetoprotein (AFP) as a marker in assessing response to systemic chemotherapy. Fifty-seven inoperable HCC patients were enrolled. The administered regimen consisted of 60 mg/m ² cisplatin on day 1 followed by 1,200 mg/m² 5-fluorouracil on days 1-4, repeated every 3 weeks. One patient achieved a complete response (1.8%) and 7 a partial response (12.3%), an overall response rate of 14.1% and a disease control rate of 43.9%. Median time to progression (TTP) was 2.4 months, and median overall survival (OS) 9.8 months. The main grade 3 and 4 toxicities were leucopenia (10.5%), neutropenia (21.0%) and thrombocytopenia (8.8%). Of the 45 patients with an initially elevated AFP level, 15 (33.3%) showed a reduction of more than 50%. The disease control rate was significantly higher in AFP responders (80.0 vs. 23.3% in AFP non-responders, p<0.001), who moreover exhibited prolonged TTP (p=0.010). Combination chemotherapy of 5-fluorouracil and cisplatin showed modest disease control activity and acceptable toxicity in patients with inoperable HCC. Furthermore, AFP response may be a useful surrogate marker for clinical outcome.