Phase II study of sorafenib plus tegafur/uracil (UFT) in patients with advanced hepatocellular carcinoma (HCC)

Abstract

15664 Background: Sorafenib, a multikinase inhibitor with anti-angiogenic and pro-apoptotic activities, has recently been approved for the treatment of advanced HCC. Combination of sorafenib with metronomic chemotherapy has theoretic advantage in improving anti-tumor activity without increasing treatment-related toxicities. UFT (tegafur: uracil = 4:1 in molar ratio) is an oral fluoropyrimidine which is active against various gastrointestinal cancers. We conducted this study to evaluate the efficacy and safety of sorafenib plus low-dose UFT in advanced HCC patients (pts). Methods: Pts with histologically or cytologically proven unresectable/metastatic HCC, ECOG PS 0–2, Child-Puch class A, platelets ≥ 100 K/μl, transaminases ≤ 5 × ULN, bilirubin ≤ 3 mg/dl, INR ≤ 2.3 and creatinine ≤ 1.5 × ULN were enrolled. Prior local treatment for HCC was allowed. Sorafenib (400 mg bid) and UFT (125 mg/m2 based on tegafur bid) were taken per os continuously. Tumor assessment was performed q8w by RECIST criteria. Primary endpoint is progression-free survival (PFS). Results: Between Apr. and Nov. of 2007, 40 pts were enrolled. 24 pts were evaluable at this interim analysis. The baseline pt characteristics were: male/female 22/2; median age 57 (range, 31–83); TNM stage IIIA/IIIC/IV 11/2/11; CLIP score all ≤3; extrahepatic metastasis 50%; major hepatic vessel/main portal vein involvement 50%/21%; prior local treatment 67%; HBsAg(+)/anti-HCV(+)/both(+) 18/6/1. Pts received a median of 15.5 (range 4–32+) weeks of treatment. Grade 3 hematologic toxicities occurred in 1 pt. Most common grade 3 non-hematologic toxicities included hand-foot skin reactions, malaise and diarrhea in 3, 4 and 2 pts, respectively. No grade 4 toxicities or any ≥ grade 3 hypertension, bleeding or thromboembolic events were noted. There were 3 (12.5%) PR and 11 (45.8%) SD, with a median PFS of 3.7 months (95% C.I., 1.7–5.7). Conclusions: The result of this interim analysis suggests that combination of sorafenib and UFT is potentially an effective regimen for pts with advanced HCC. The toxicities observed were manageable. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer