A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.

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354 Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.