Kinase inhibitor approved for GIST and advanced renal cell carcinoma
SutentSunitinibPFIZERKinase inhibitor approved for GIST and advanced renal cell carcinoma
This small molecule inhibits multiple receptor tyrosine kinases (RTK), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was approved on January 26, 2006, for the treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib and for the treatment of advanced renal cell carcinoma.
Efficacy. The efficacy of sunitinib in the treatment of GIST was evaluated in a randomized, double-blind, placebo-controlled trial. The intent-to-treat (ITT) population included 312 patients who were randomized to receive either 50 mg of sunitinib or placebo orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2). Patients receiving sunitinib experienced a median time to tumor progression (TTP) of 27.3 weeks versus 6.4 weeks for patients receiving placebo (P<.0001). Median progression free survival was 24.1 weeks in the sunitinib arm versus 6.0 weeks in the placebo arm (P<.0001). The efficacy of sunitinib in the treatment of cytokine-refractory metastatic renal cell carcinoma (MRCC) was evaluated in 2 single-arm, multicenter studies. Objective response rate (ORR) and duration of response (DR) were evaluated in both studies. In Study 1 (N=106), the ORR was 25.5% and the median DR was 27.1 weeks. In Study 2 (N=63), the ORR was 36.5% and the median DR was 54 weeks.
Dosing. The recommended dose of sunitinib for GIST and advanced renal cell carcinoma is one 50-mg oral dose taken once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off. The drug may be taken with or without food. Dose increase or reduction in 12.5-mg increments is recommended based on individual safety and tolerability. As strong CYP3A4 inhibitors such as ketoconazole may increase sunitinib plasma concentrations, a dose reduction of sunitinib to a minimum of 37.5 mg daily should be considered if the drugs are coadministered. Since CYP3A4 inducers such as rifampin may decrease sunitinib plasma concentrations, a dose increase of sunitinib to a maximum of 87.5 mg daily should be considered if the drugs are coadministered.