A phase I study of sunitinib malate (SU11248) in combination with gefitinib in patients with metastatic renal cell carcinoma (mRCC)

4537 Background: Sunitinib malate (SU11248) is an oral multitargeted tyrosine kinase inhibitor of VEGF and PDGF receptors. Two phase II trials with sunitinib given as second line therapy in patients with mRCC showed a ≥40% response rate (JCO 2006;24:16–24; Proc ASCO 23,380s). Combining sunitinib and gefitinib (an EGFR inhibitor) may enhance antitumor activity by providing a broader spectrum of tyrosine kinase inhibition. The maximum tolerated dose (MTD) of sunitinib in combination with gefitinib was assessed in this Phase I trial. Methods: Patients with mRCC previously treated with cytokine therapy were enrolled in the study. Cohorts of 4–6 patients received escalating doses of sunitinib and a fixed dose of gefitinib. Dose levels of sunitinib were 37.5 mg and 50 mg. Dose limiting toxicity (DLT) was defined as Grade 4 hematologic toxicity, Grade 3 nonhematologic toxicity of ≥7 days or a Grade 2 cardiac toxicity. Six-week treatment cycles comprised of sunitinib daily for 4 weeks followed by 2 weeks off and ...