A phase II study of sunitinib in advanced hepatocellular carcinoma

BackgroundIn 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma.AimIn 2005 we designed a phase II study to assess safety and efficacy of sunitinib.MethodsThis 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 50 mg each day orally, 4 weeks on, 2 weeks off.ResultsBetween 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.ConclusionA dose of 50 mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5 mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders.