The Current Status and Evolving Role of Sunitinib in Non-small Cell Lung Cancer

Sunitinib, a small molecule, is a multitargeted receptor kinase inhibitor which targets the vascular endothelial growth factor receptor and platelet-derived growth factor receptor as well as several others. Initially approved for the treatment of renal cell carcinoma as well as imatinib-resistant gastrointestinal stromal tumors, the activity of sunitinib has been explored in several other solid tumors including non-small cell lung cancer (NSCLC). An initial phase II trial in 63 previously treated NSCLC patients using a dose of 50 mg daily 4 of 6 weeks showed a response rate of 11.1% and a stable disease rate of 26.8%. The median time to disease progression and overall survival was 12.0 and 23.4 weeks, respectively. The principal toxicities included fatigue, pain, myalgias, nausea/vomiting, and hypertension. Three hemorrhagic deaths were reported (two pulmonary and one central nervous system). After this trial was completed, a subsequent sequential cohort of 47 previously treated NSCLC patients were treated on a continuous dosing schedule of sunitinib at 37.5 mg daily. A response rate of 2.1% was reported with a stable disease rate of 19.X%. The median time to progression was 12.3 weeks with a median survival time of 38.1 week. Toxicities were, in general, less frequent and similar to those noted in the initial trial. Sunitinib is currently being evaluated in combination with a number of standard regimens commonly used in NSCLC as well as a maintenance drug after first-line platinum-based treatment of advanced NSCLC. Results of these trials are eagerly awaited and will help define the role of sunitinib in the therapeutic approach to NSCLC.