title: Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy.
abstract: OBJECTIVE
  Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti-VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS.
  
  
  METHODS
  Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately.
  
  
  RESULTS
  Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T(1)), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2).
  
  
  CONCLUSIONS
  Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients.
authors.affiliation: Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Uldrick
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.forename: Pallavi
authors.initials: P
authors.lastname: Kumar
authors.forename: Deirdre
authors.initials: D
authors.lastname: O'Mahony
authors.forename: Wendy
authors.initials: W
authors.lastname: Bernstein
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Vickie
authors.initials: V
authors.lastname: Marshall
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
authors.forename: Richard F
authors.initials: RF
authors.lastname: Little
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000068258:Bevacizumab; D016207:Cytokines / Q000097:blood; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008396:Maryland; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D044966:Anti-Retroviral Agents; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab