Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
Title | Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Escudier, B., Roigas J., Gillessen S., Harmenberg U., Srinivas S., Mulder S. F., Fountzilas G., Peschel C., Flodgren P., Maneval E. Chow, Chen I., & Vogelzang N. J. |
Journal | J Clin Oncol |
Volume | 27 |
Issue | 25 |
Pagination | 4068-75 |
Date Published | 2009 Sep 1 |
ISSN | 1527-7755 |
Keywords | Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Renal Cell, Cytokines, Disease-Free Survival, Drug Administration Schedule, Drug Resistance, Neoplasm, Europe, Female, Humans, Indoles, Kaplan-Meier Estimate, Kidney Neoplasms, Male, Middle Aged, Protein Kinase Inhibitors, Pyrroles, Quality of Life, Time Factors, Treatment Outcome, United States |
Abstract | 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. |
DOI | 10.1200/JCO.2008.20.5476 |
Alternate Journal | J. Clin. Oncol. |
PubMed ID | 19652072 |