Phase II trial of sorafenib and capecitabine for hepatocellular carcinoma in cirrhotic patients.

Abstract

341 Background: Sorafenib (sorf.) has become the standard treatment for Hepatocellular Carcinoma (HCC), demonstrating an increase in patients (pts) median survival from 7.9 to 10.7 months (m) (Llovett, NEJM 2008). Abou-Alfa added doxorubicin to sorf. observing a median survival of 13.7 m vs 6.7 m. for doxorubicin + placebo, (JAMA. 2010). Since most of our HCC pts were cirrhotic and 8/12 HCV +, and 2/12 HBV only +, with cirrhosis and thrombopenia we chose to add capecitabine (cap) to sorf in a phase II trial, anticipating better tolerance. Primary objectives were to assess safety and tolerability of the combination while secondary objectives included estimations of PFS, OST and documentation of disease control rate (DCR = CR+PR+SD). With relaxation of eligibility criteria C-P B-7 pts and ≥ 50,000 platelets were allowed. Methods: Sorf dose was 400 mg BID with dose adjustments for sorf related hand foot syndrome (HFS). Starting cap dose was 850mg/m2 BID x 7 Q 14 and adjusted as tolerated to 650mg/m2 BID or to 500 mg/m2 BID x 7 Q 14.. The lowest dose used was 250 mg/m2; BID (500 mg BID) for 5 days Q14. Patients: Only 12 of about 30 assessed patients met eligibility criteria, and were recruited between Nov. 2, 2009 and Sep. 13, 2011.The protocol was reviewed and approved by the WIRB and all participants signed an IRB approved consent form. Results: Preliminary Results: Eight of 12 patients are alive, survivals ranging from 2.5 to 23 m. One patient has an unmaintained radiological CR continuing for 23 months with an AFP decrease from 139 to 2.9. Another patient had a PR and an AFP decrease from 355 to 3.2 ng/mL. She died in PR at 13 months from an UGI bleed. Grade 3 and 4 toxicities were limited to the skin, and included HFS, in 4/12, skin ulcers at sites of prior osteomyelitis (1/12); requiring treatment cessation, and fatigue in 4 /12. Conclusions: With meticulous attention to cap dose adjustments as dictated by HFS this combination can be tolerated longitudinally in these frail pts that are not candidates for adding more aggressive agents to sorf. The objective radiological responses corroborated by AFP decreases in this very small cohort suggest that the findings are real, and warrant expansion of the trial.