Originally published as JCO Early Release 10.1200/JCO.2008.20.5476 on August 3 2009

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Phase II Study of Sunitinib Administered in a Continuous Once-Daily Dosing Regimen in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma

From the Institut Gustave Roussy, Villejuif, France; Charité-Universitätsmedizin, Berlin; Klinikum rechts der Isar, Munich, Germany; Kantonsspital St Gallen, St Gallen, Switzerland; Karolinska University Hospital, Stockholm; Lund University Hospital, Lund, Sweden; Stanford University, Stanford, CA; Pfizer Global Research and Development, La Jolla, CA; Nevada Cancer Institute, Las Vegas, NV; Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and the Papageorgiou Hospital, Thessaloniki, Greece.

Corresponding author: Bernard Escudier, MD, Unité Immunothérapie, Institut Gustave Roussy; 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France; e-mail: bernard.escudier{at}igr.fr.

Purpose Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen.

Patients and Methods Eligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures.

Results One hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM.

Conclusion Sunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.

Supported by Pfizer Inc.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL, and at the 14th European Cancer Conference, September 23-27, 2007, Barcelona, Spain.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00137423 [ClinicalTrials.gov] .

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