A phase II study of sunitinib in advanced hepatocellular carcinoma.

Abstract: Background: In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma. Aim: In 2005 we designed a phase II study to assess safety and efficacy of sunitinib. Methods: This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0–1; and Child≤B8. The treatment schedule was 50mg each day orally, 4 weeks on, 2 weeks off. Results: Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months. Conclusion: A dose of 50mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders. [Copyright &y& Elsevier]