Objective: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. Design: A randomized controlled trial. Setting: A tertiary referral center. Patients: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. Intervention: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m(2) each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. Main Outcome Measures: Recurrence rate and disease-free survival. Results: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20 %) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P = .01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P = .03). The respective disease-free survival rates at 1, 2, and 3 years were 50 %, 36 %, and 18 % for the treatment group and 69 %, 53 %, and 48 % for the control group (P=.04). Conclusion: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.
