Chung-Han Lee1, Robert J Motzer2. 1. Genito-urinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY. 2. Genito-urinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: motzerr@mskcc.org.
Abstract
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.
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.
Authors: Frank Hilberg; Ulrike Tontsch-Grunt; Anke Baum; Anh T Le; Robert C Doebele; Simone Lieb; Davide Gianni; Tilman Voss; Pilar Garin-Chesa; Christian Haslinger; Norbert Kraut Journal: J Pharmacol Exp Ther Date: 2017-12-20 Impact factor: 4.030