A randomized study of cisplatin and 5-FU hepatic arterial infusion chemotherapy with or without adriamycin for advanced hepatocellular carcinoma

Purpose: This multicenter, randomized, open-labeled, clinical trial evaluated the efficacy and safety of cisplatin/5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (CF-HAIC) versus adriamycin adding to CF-HAIC (ACF-HAIC) in advanced HCC patients. Methods: Fifty-six patients with advanced HCC were randomized to two treatment groups: (1) CF-HAIC group [n = 29, 5-FU, 500 mg/m² on days 1-3, and cisplatin, 60 mg/m² on day 2] and (2) ACF-HAIC group [n = 27, adriamycin, 50 mg/m² on day 1, 5-FU, 500 mg/m² on days 1-3, and cisplatin, 60 mg/m² on day 2] every 4 weeks via an implantable port system. Primary efficacy endpoint was overall survival (OS). Treatment response and time to progression were secondary endpoints. Results: Treatment response rates did not differ significantly between the two treatment groups. Time to progression (5.4 vs. 5.8 months, P = 0.863) and OS (11.1 vs. 8.8 months, P = 0.448) were not significantly different. When the factors affecting patient OS were analyzed, disease control rate [P < 0.001, HR 6.437 (95 % CI 2.580-16.064)] was independently associated with OS. Age (≥60 years) and serum AFP level (≥200 ng/dL) also were significant factors for OS [P = 0.007, HR 4.945 (95 % CI 1.543-15.850), P = 0.048, HR 2.677 (95 % CI 1.010-7.095), respectively]. Grade 4 treatment-related toxicity and mortality was not observed in both groups. Conclusions: Although both HAIC regimens are safe and effective in patients with advanced HCC, HAIC adding adriamycin did not show delayed tumor progression and survival benefit compared to CF-HAIC in advanced HCC.