A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma.

PURPOSE: Patients with advanced hepatocellular carcinoma (HCC) have few treatment options. Thymalfasin (thymosin α-1) is an immunomodulator that may increase response to ablative therapy through direct anti-tumor action or enhanced protection against infections. We compared transarterial chemoembolization (TACE) plus thymalfasin with TACE alone for unresectable HCC. METHODS: In this phase II, randomized trial, 25 patients received either TACE plus thymalfasin (1.6 mg SC, 5 times weekly; n = 14) or TACE alone (n = 11) for 24 weeks. Response was defined as transition to transplant eligibility or lack of disease progression through week 72. Survival was assessed through 24 months post-treatment. RESULTS: Eight of fourteen (57.1%) patients in the TACE + thymalfasin group versus 5 of 11 (45.5%) patients in the TACE-only group became responders (P = 1.0). Four of fourteen TACE + thymalfasin patients versus none of 11 TACE-only patients became eligible for transplant. Median overall survival time was 110.3 weeks for the TACE + thymalfasin group versus 57.0 weeks for the TACE-only group (P = 0.45). Seven patients in each group experienced serious adverse events; there were no bacterial infections in the TACE + thymalfasin group versus 4 in the TACE-only group. There were 3 deaths in the TACE + thymalfasin group and 5 in the TACE-only group. CONCLUSIONS: In patients with unresectable HCC, TACE + thymalfasin resulted in numerically higher rates of survival and tumor response, including transplant candidacy, with fewer bacterial infections, than TACE alone. Treatment regimens for HCC including thymalfasin as an immunomodulator should be evaluated in larger trials.