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Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab†
Article first published online: 30 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 23, pages 5383–5390, 1 December 2010
How to Cite
Garcia, J. A., Hutson, T. E., Elson, P., Cowey, C. L., Gilligan, T., Nemec, C., Dreicer, R., Bukowski, R. M. and Rini, B. I. (2010), Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab. Cancer, 116: 5383–5390. doi: 10.1002/cncr.25327
Presented in part at the ASCO Genitourinary Cancer Symposium, San Francisco, California, February 14-16, 2008 (Abstract 346), and American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30-June 3, 2008 (Abstract 5123).
- Issue published online: 23 NOV 2010
- Article first published online: 30 AUG 2010
- Manuscript Accepted: 13 JAN 2010
- Manuscript Revised: 11 JAN 2010
- Manuscript Received: 5 NOV 2009
- metastatic renal cell carcinoma refractory;
Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab- or sunitinib-refractory mRCC have not been prospectively investigated.
Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)-defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was permitted in the absence of significant toxicity. The primary endpoint was tumor burden reduction rate, defined as the proportion of patients with ≥5% reduction in the sum of RECIST-defined target lesions without other PD. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival, and safety. A 2-stage accrual design was used to test the alternative hypothesis that the tumor burden reduction rate was >20% versus <5%.
Forty-eight patients were enrolled. The tumor burden reduction rate was 30% (95% confidence interval [CI], 17%-45%). One unconfirmed objective partial response was observed. The median PFS was 4.4 months (95% CI, 3.6-5.9). There was no association of PFS and tumor shrinkage with response to prior therapy. Most treatment-related adverse events were of mild-to-moderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (P = .03) and mucositis (P = .06), whereas sunitinib-treated patients tended to develop more skin rash (P = .06).
Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factor-targeted therapy in mRCC. Cancer 2010. © 2010 American Cancer Society.