Uracil-tegafur as an adjuvant for hepatocellular carcinoma: A randomized trial

Abstract

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n ‫؍‬ 79, UFT group) or surgery alone (n ‫؍‬ 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P ‫؍‬ .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P ‫؍‬ .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P ‫؍‬ .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P ‫؍‬ .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival. (HEPATOLOGY 2006;44:891-895.)

Adjuvant chemotherapy with tegafur/uracil administration after transcatheter arterial chemoembolization for advanced hepatocellular carcinoma

“…In contrast to our result, Hasegawa et al recently reported that there was no evidence to support the potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC (31). These apparently paradoxical results may be attributed to the difference in the target.…”

Adjuvant Intraarterial Injection of 131I-Labeled Lipiodol After Resection of Hepatocellular Carcinoma: Progress Report of a Case-Control Study with a 5-Year Minimal Follow-up

“…Treatment with retinoids gave the same results and prevented second HCC tumors after surgical resection or radiofrequency therapy (6). Systemic chemotherapy, contrary to what is observed in some other digestive cancers, did not decrease this risk (16)(17)(18). Early recurrences due to the removed cancer could be prevented by treatments delivered in the hepatic artery (19); in this setting, chemoembolization seems of interest (20).…”

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Theoretically, adjuvant chemotherapy may reduce or delay such recurrence, but few chemotherapeutic agents have been shown to be effective against HCC and not a few of them may be hepatotoxic. Hasegawa et al [406] reported an RCT using oral administration of uraciltegafur after curative hepatic resection but found no beneficial effects on recurrence and a possible adverse effect on overall survival. In 1966, Muto et al [407] reported that administration of polyprenoic acid, an acyclic retinoid, reduced recurrence of HCC in an RCT.…”