The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery.

Rini, Brian I; Garcia, Jorge; Elson, Paul; Wood, Laura; Shah, Shetal; Stephenson, Andrew; Salem, Mohammed; Gong, Michael; Fergany, Amr; Rabets, John; Kaouk, Jihad; Krishnamurthi, Venkatesh; Klein, Eric; Dreicer, Robert; Campbell, Steven

PURPOSE We investigated the effect of sunitinib on locally advanced primary renal carcinoma tumors and the ability to facilitate subsequent surgery. MATERIALS AND METHODS Patients with an unresectable primary renal tumor, with or without distant metastases, received 50 mg sunitinib with continuous daily dosing in a phase II trial. Computerized tomography was performed every 12 weeks to determine surgical resectability. The primary end point of the trial was the percentage of patients with renal cell carcinoma and initially unresectable primary tumors who could undergo nephrectomy after sunitinib therapy. RESULTS Of 30 patients enrolled in the study (19 with distant metastases) 28 (35 total renal tumors) were evaluable for response. The median change in primary renal cell carcinoma tumors was a 22% decrease, corresponding to a median absolute reduction of 1.2 cm. The median reduction in primary renal cell carcinoma tumors of clear cell histology was -28% (absolute reduction 1.7 cm) compared to a 1.4% increase (0.1 cm absolute increase) in nonclear cell tumors. Of these patients 13 (45%) met the primary end point of being able to undergo nephrectomy after preoperative sunitinib. All patients had viable renal cell carcinoma in the surgical specimen and surgical morbidity was consistent with prior experience of nephrectomy in patients without preoperative therapy. CONCLUSIONS Sunitinib as initial therapy in patients with locally advanced features of the primary tumor was feasible and resulted in an antitumor effect that enabled subsequent surgery in a subset of patients. Further prospective study is required to refine the most suitable application of this approach.