title: A phase II study of bevacizumab and high-dose interleukin-2 in patients with metastatic renal cell carcinoma: a Cytokine Working Group (CWG) study.
abstract: 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.
authors.affiliation: *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.
authors.forename: Uday B
authors.initials: UB
authors.lastname: Dandamudi
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.forename: Todd S
authors.initials: TS
authors.lastname: Crocenzi
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Curti
authors.forename: Ulka N
authors.initials: UN
authors.lastname: Vaishampayan
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Crosby
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007376:Interleukin-2; D000068258:Bevacizumab