Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer

© 2009 by American Society of Clinical Oncology Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer Giuseppe Di Lorenzo, Giacomo Cartenì, Riccardo Autorino, Gianni Bruni, Marianna Tudini, Mimma Rizzo, Michele Aieta, Antonio Gonnella, Pasquale Rescigno, Sisto Perdonà, Gianluca Giannarini, Sandro Pignata, Nicola Longo, Giovannella Palmieri, Ciro Imbimbo, Michele De Laurentiis, Vincenzo Mirone, Corrado Ficorella and Sabino De Placido + Author Affiliations From the Dipartimento di Endocrinologia ed Oncologia Clinica e Molecolare, and Sezione di Urologia, Università Federico II; Unità Operativa Complessa (UOC) Oncologia, Ospedale Cardarelli; Clinica Urologica, Seconda Università degli Studi; UOC Oncologia Urologica, INT Fondazione “G. Pascale”, Napoli; UO Oncologia, Università Dell'Aquila, L'Aquila; Unità Operativa (UO) Oncologia Ospedale Oncologico Regionale, Rionero in Vulture, Potenza; and UO Urologia Universitaria, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. Corresponding author: Giuseppe Di Lorenzo, MD, PhD, Dipartimento di Endocrinologia ed Oncologia Clinica e Molecolare, Università Federico II, Napoli, Italy; e-mail: giuseppedilorenzoncol@hotmail.com. Abstract Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients. Footnotes Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. Received February 20, 2009. Accepted April 8, 2009. CiteULikeConnotea