Effect of sofosbuvir and ribavirin on therapeutic efficacy of sorafenib in the treatment of hepatocellular carcinoma

Abstract

Background: Advanced and unresectable hepatocellular carcinoma (HCC) carries a poor prognosis and systemic therapy provides marginal benefits. Most of the patients diagnosed as HCC are hepatitis C positive with no prior anti viral treatment. Sorafenib is standard of treatment for unresectable HCC with marginal survival benefit. The hypothesis that anti viral therapy with sofosbuvir and ribavirin could regress HCC in patients on sorafenib. This clinical study examined whether sofosbuvir and ribavirin improves the therapeutic efficacy of sorafenib in patients with advanced HCC in terms of tumor response, time to progression, one year survival and quality-of-life. Methods: All HCC patients with Child Puge Aand B, ECOG performance status 1 & 2 with hepatitis C positive and no history of prior chemotherapy and anti viral therapy. The treatment included oral administration of Sofosbuvir 400mg daily with Ribavirin 500mg twice daily and Sorafenib 400 mg daily was given between October 2016 to March 2017. AFP level was done monthly with CT scan 3 monthly for response assessment. Tumor response by Response Evaluation Criteria in Solid Tumors (RECIST), toxicity by Common Toxicity Criteria (CTC) version 4.0. Results: Total 40 patients were recruited in this study. 10 patients stopped anti viral therapy due to poor tolerance. 30 patients completed their 6 month treatment. Significant disease reduction was seen after resolution of Hepatitis C with fall in AFP level. Overall 15 patients (50%) showed partial response (PR) and 12 patients (40%) had stable disease (SD) with 10% progressive disease (PD). Grade 3 fatigue, abdominal pain and vomiting was observed in 5% cases, but Grade 1 and 2 fatigue, nausea abdominal pain and anorexia was seen in almost all patients. Rest of 10 patients who did not tolerate the anti viral therapy were expired after 2 month of targeted therapy. Conclusions: This study clearly showed that resolution of Hepatitis C infection can increase the efficacy of anti cancer treatment in HCC as compared to those patient with high infection load. One year survival will be assessed after completion of time.