Researchers from France have reported that treatment with Sutent® (sunitinib) of patients with advanced hepatocellular carcinoma was associated with a low response rate and significant toxicity. The details of this study appeared in an early online publication in Lancet Oncology on July 7, 2009.[1] 

Sutent is an oral kinase inhibitor of fms-like tyrosine kinase 3 (Flt3), Kit, VEGF, and PDGF receptors that is currently in clinical trials for treatment of a variety of malignancies. It produces anticancer effects through targeted mechanisms that include anti-angiogenesis, as well as direct killing of the cancer cell. In Phase I-II studies, Sutent demonstrated anti-tumor and anti-angiogenic activity in renal cell carcinoma, as well as other solid tumors. In January 2006 the U.S. Food and Drug Administration approved the use of Sutent for the treatment of gastrointestinal stromal tumors that had progressed after Gleevec® (imatinib mesylate) and for advanced renal cell carcinoma. More recent studies have suggested that Sutent is active for the treatment of pancreatic islet cell cancer and non–small cell lung cancer.

A total of 37 patients were enrolled in this clinical trial with only one patient having a partial response. However, 35% of patients achieved stable disease for over three months. Common side effects included thrombocytopenia, neutropenia, anemia, and hand-foot syndrome. There were four deaths possibly related to toxicity of treatment.

Comments: These results did not meet the preset criteria for effectiveness, and treatment was associated with significant toxicity. These results are disappointing, as other similar targeted agent appear to be active in hepatocellular carcinoma. It is possible that other doses and schedules of Sutent will be studied in this disease.