Final Results of a Randomized Phase II Study of TSU-68 after Transarterial Chemoembolisation in Japanese Patients with Unresectable Hepatocellular Carcinoma.Chemoembolization

ABSTRACT Purpose TSU-68 is an antitumor drug that acts by inhibiting angiogenesis. We evaluated the efficacy and safety of TSU-68 in combination with transcatheter arterial chemoembolization (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC). Methods In this multicenter, open-label phase II study, we randomly assigned patients with HCC who had been treated by TACE to receive either 200 mg TSU-68 twice daily or no medication. TACE was performed according to the standard technique using anticancer drugs, lipiodol, and gelatin sponge. TACE was completed for all patients within the 2 weeks prior to randomization. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were safety and biomarker assessments. Results In total, 103 patients were enrolled. Median PFS was 5.2 months in the TSU-68 group and 4.0 months in the control group (HR in the TSU-68 group, 0.699; p = 0.054, log-rank test with a 2.5% one-sided significance level). Fatigue, elevated aspartate aminotransferase (AST), elevated alkaline phosphatase, edema, and anorexia were more frequent in the TSU-68 group than in the control group. The most frequent grade 3/4 adverse events were AST elevation (46% of patients in the TSU-68 group and 12% of controls) and alanine aminotransferase elevation (26% of patients in the TSU-68 group and 8% of controls). Subgroup analyses suggested that treatment with TSU-68 may extend PFS for patients with Child–Pugh A liver function and those with hepatitis C. Among patients with baseline t-PA concentrations below the median value, the PFS of the TSU-68 group was longer than that of the control group. TSU-68 treatment may also improve PFS among patients with VCAM-1, ELAM-1, IL-8, or PDGF-BB levels above the median values. Conclusion TSU-68 was well tolerated, and may provide longer PFS after TACE than was observed for controls. This result suggests that TSU-68 combined with sequential and repeated TACE sessions may provide additional clinical benefits to patients, including prolongation of overall survival. A randomized placebo-controlled phase III global study was initiated in 2010 to evaluate the survival benefit of TSU-68 in combination with repeated TACE. Disclosure All authors have declared no conflicts of interest.