Background: Hepatocellular carcinoma (HCC) tumour spread is partly dependent on neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties, was assessed in patients with advanced unresectable HCC. Methods: Between February and July, 2006, eligible patients were enrolled and treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment). The primary endpoint of this Simon two-stage phase II trial was objective response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with an expected response rate of 15%. This trial is registered with ClinicalTrials.gov, number NCT00247676. Findings: Of 37 patients enrolled, one (2·7%) patient experienced a confirmed partial response, giving an overall objective response rate of 2·7% (95% CI 0·1-14·2); on the basis of this, the trial did not proceed to the second stage. 13 (35%) of 37 patients achieved stable disease for over 3 months. Commonly observed grade 3 and 4 adverse events included thrombocytopenia (14 of 37; 37·8%), neutropenia (nine of 37; 24·3%), asthenia (five of 37; 13·5%), hand-foot syndrome (four of 37; 10·8%), and anaemia (four of 37; 10·8%). There were four deaths among the 37 patients (10·8%) that were possibly related to treatment. Interpretation: Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC. The response rate was low, and the study did not meet the primary endpoint based on RECIST criteria. Funding: Pfizer Oncology.
Bibliographical noteFunding Information:
SF, ER, JD, and ALC have been compensated as consultants and advisers to Pfizer Inc. SF, ER, and ALC have received research funding from Pfizer Inc. SL, XL, CH, AR-G, and MJL are employees of Pfizer Oncology. SL, XL, SD, a close family member of CH, and MJL, own stock in Pfizer Inc. ALC has received honoraria from Pfizer Inc. EB, HYL, JSK, and MZ declared no conflicts of interest.
The study was sponsored by Pfizer Oncology. Editorial assistance was provided by Christine Arris (ACUMED), funded by Pfizer Oncology. We thank S Pitman-Lowenthal for medical expertise. We also acknowledge L Sherman and K Letrent for their input into the study and their comments on the manuscript.
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