Sorafenib.
OBJECTIVE
Sorafenib is an oral, multikinase inhibitor that was recently approved for use in metastatic renal cancer. It is currently undergoing investigation in locally advanced renal cancer and in other tumor types.


RESULTS
Sorafenib was initially developed as an inhibitor of Raf kinase; however, it has broad spectrum activity against multiple tyrosine kinases, including angiogenic factors VEGFR and PDGFR. Common toxicities experienced with sorafenib include hypertension, hand-foot syndrome, rash, diarrhea and fatigue. Early clinical trials suggested that sorafenib acts as a cytostatic agent, as many patients experienced prolonged disease stabilization but insufficient tumor shrinkage to meet RECIST criteria for response. To assess whether sorafenib's growth inhibition translated into a clinical benefit, a phase II randomized discontinuation trial was designed. This trial demonstrated that sorafenib increased progression-free survival in patients with metastatic renal cell cancer; the phase II data were confirmed in a large international phase III trial.


CONCLUSIONS
In this review, we will discuss the clinical development of sorafenib and its role in the treatment of renal cancer. Additionally, we will highlight critical methods of clinical trial design and biomarker development that contribute to the development of sorafenib.
Hahn
Olwen
O
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Illinois 60637, USA.
Stadler
Walter
W
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor