732P - Final results of a randomized phase II study of TSU-68 after transarterial chemoembolisation in Japanese patients with unresectable hepatocellular c...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anticancer agents
Hepatobiliary Cancers
Therapy
Biological therapy
Presenter Shuichi Kaneko
Authors S. Kaneko1, Y. Inaba2, F. Kanai3, T. Aramaki4, T. Yamamoto5, T. Tanaka6, K. Yamakado7, M. Kudo8, K. Imanaka9, Y. Arai10
  • 1Department Of Gastroenterology, Kanazawa University Hospital, 920-8641 - Ishikawa/JP
  • 2Diagnostic And Interventional Radiology, Aichi Cancer Center Hospital, 464-8681 - Aichi/JP
  • 3Gastroenterology, Chiba University Hospital, 260-8677 - Chiba/JP
  • 4Diagnostic Radiology, Shizuoka Cancer Center Hospital, 411-0934 - Shizuoka/JP
  • 5Diagnostic Imaging, Tochigi Cancer Center, 320-0834 - Tochigi/JP
  • 6Radiology, Nara Medical University Hospital, 634-8522 - Nara/JP
  • 7Radiology, Mie University Hospital, 514-8507 - Mie/JP
  • 8Gastroenterology And Hepatology, Kinki University Hospital, 589-8511 - Osaka/JP
  • 9Hepatobiliary And Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 537-8511 - Osaka/JP
  • 10Diagnostic Radiology, National Cancer Center Hospital, 104-0045 - Tokyo/JP

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.