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A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer†
Article first published online: 20 MAR 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 11, pages 2438–2446, 1 June 2009
How to Cite
Amato, R. J., Jac, J., Giessinger, S., Saxena, S. and Willis, J. P. (2009), A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer, 115: 2438–2446. doi: 10.1002/cncr.24280
Presented in part at the 2006 and 2007 Annual Meetings of the American Society of Clinical Oncology, Atlanta, Georgia, June 2-6, 2006, and Chicago, Illinois, June 1-5, 2007.
- Issue published online: 20 MAY 2009
- Article first published online: 20 MAR 2009
- Manuscript Accepted: 17 NOV 2008
- Manuscript Revised: 11 NOV 2008
- Manuscript Received: 9 OCT 2008
- renal cell cancer;
- kidney cancer;
- mammalian target of rapamycin (mTOR);
- drug therapy
Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, affects tumor growth by blocking growth factor stimulation, arresting cell cycle progression, and inhibiting angiogenesis. mTOR inhibitors and agents with primarily antiangiogenic activity have been shown to have efficacy in renal cell cancer (RCC). This phase 2 study assessed the efficacy of daily oral dosing with everolimus in patients with RCC.
Patients had confirmed predominantly clear cell RCC; had received ≤1 prior therapy; and had progressive, measurable metastatic disease. Everolimus was given at a dose of 10 mg daily orally without interruption (28-day cycle), with dose modifications for toxicity (graded according to National Cancer Institute Common Toxicity Criteria, version 3.0). Patients were evaluated every 2 cycles (8 weeks) using Response Evaluation Criteria in Solid Tumors (RECIST).
Of 41 enrolled patients, 39 were treated and evaluable for safety, 37 of whom were evaluable for response (2 patients withdrew after the first week of therapy). Approximately 78% of the patients were male, the median age was 60 years, 93% had a Zubrod performance status of 0 to 1, and 83% had received prior therapy. The median progression-free survival (PFS) was 11.2 months and the median overall survival was 22.1 months. Partial responses were observed in 5 (14%) patients, stable disease lasting ≥3 months was reported in 27 (73%) patients, and stable disease lasting ≥6 months was reported in 21 (57%) patients. Nausea (38% of patients), anorexia (38% of patients), diarrhea (31% of patients), stomatitis (31% of patients), pneumonitis (31% of patients), and rash (26% of patients) were common. Grade 3 of 4 adverse events included pneumonitis (18% of patients); transaminase elevations (10% of patients); thrombocytopenia, hyperglycemia, and alkaline phosphatase elevations (8% each of patients); and hyperlipidemia (5% of patients).
In the current study, everolimus demonstrated encouraging antitumor activity against metastatic RCC as indicated by a PFS ≥ 6 months for approximately 70% of patients. Cancer 2009. © 2009 American Cancer Society.