Overexpression of vascular endothelial growth factor in renal cell carcinoma (RCC) leads to angiogenesis, tumor progression, and inhibition of immune function.
We conducted the first phase II study to estimate the efficacy and safety of bevacizumab with high-dose interleukin-2 (IL-2) therapy in patients with metastatic RCC. Eligible patients had predominantly clear cell metastatic RCC, measurable disease, a Karnofsky Performance Status of ≥80%, and adequate end-organ function. IL-2 (600,000 IU/kg) was infused intravenously every 8 hours (maximum 28 doses) during two 5-day cycles on days 1 and 15 of each 84-day course. Bevacizumab (10 mg/kg) was infused intravenously every 2 weeks beginning 2 weeks before initiating IL-2. Fifty of 51 eligible patients from 8 centers were enrolled. Median progression-free survival (PFS) was 11.2 months (90% confidence interval, 5.7-17.7), and 2-year PFS was 18% (90% confidence interval, 8%-27%). Responses included 4 complete (8%) and 11 partial (22%) responses. Toxicities did not exceed those expected from each agent alone. Combining IL-2 plus bevacizumab is feasible, with a response rate and PFS at least as high as reported previously for the single agents. The regimen did not appear to enhance the rate of durable major responses over that of IL-2 alone.
Written by:
Dandamudi UB, Ghebremichael M, Sosman JA, Clark JI, McDermott DF, Atkins MB, Dutcher JP, Urba WJ, Regan MM, Puzanov I, Crocenzi TS, Curti BD, Vaishampayan UN, Crosby NA, Margolin KA, Ernstoff MS. Are you the author?
Dartmouth Hitchcock Medical Center, Lebanon, NH; Dana-Farber Cancer Institute, Harvard School of Public Health; Beth Israel Deaconess Medical Center; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Vanderbilt University Medical Center, Nashville, TN; Loyola University Medical Center, Maywood, IL; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; St. Luke's Roosevelt Hospital Center, New York, NY; Earle A. Chiles Research Institute; Providence Cancer Center, Portland, OR; Department of Oncology, Wayne State University, Karmanos Cancer Institute, Detroit, MI; Division of Oncology, Department of Medicine, University of Washington, Seattle Cancer Care Alliance, Seattle, WA.
Reference: J Immunother. 2013 Nov-Dec;36(9):490-5.
doi: 10.1097/CJI.0000000000000003
PubMed Abstract
PMID: 24145360
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