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

被引:165
作者
Escudier, Bernard [1 ]
Roigas, Jan
Gillessen, Silke
Harmenberg, Ulrika
Srinivas, Sandhya
Mulder, Sasja F.
Fountzilas, George
Peschel, Christian
Flodgren, Per
Maneval, Edna Chow
Chen, Isan
Vogelzang, Nicholas J.
机构
[1] Inst Gustave Roussy, Unite Immunotherapie, F-94805 Villejuif, France
关键词
ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; ANEMIC CANCER-PATIENTS; QUALITY-OF-LIFE; INTERFERON ALPHA-2A; DOSE INTERLEUKIN-2; FACTOR ANTIBODY; FACTOR RECEPTOR; SU11248; TRIAL;
D O I
10.1200/JCO.2008.20.5476
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:4068 / 4075
页数:8
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