Sunitinib as a paradigm for tyrosine kinase inhibitor development for renal cell carcinoma.

Overview

OBJECTIVES: To describe the drug development and regulatory approval process for tyrosine kinase inhibitors in renal cell carcinoma using sunitinib as a model drug. METHODS AND MATERIALS: Key findings from pivotal clinical trials that contributed to regulatory approval and drug development were reviewed. RESULTS: The pathway of development for sunitinib starts from preclinical models to a phase I clinical trial followed by 2 phase II clinical trials for Food and Drug Administration accelerated approval and a phase III clinical trial for Food and Drug Administration standard approval. After standard approval, optimal dosing and use in the adjuvant setting were further explored. As an established first-line therapy for renal cell carcinoma, sunitinib is now used as a comparator arm for other drugs. CONCLUSIONS: The development of sunitinib is a model example of "bench to bedside" work in renal cell carcinoma and may provide a framework for the development of other drugs.