title: A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is a proangiogenic molecule produced by melanoma cells. We hypothesized that administration of bevacizumab (Bev), a monoclonal antibody that neutralizes VEGF, with low-dose interferon alfa-2b (IFN-alpha2b), an inhibitor of basic fibroblast growth factor (FGF), would lead to the regression of metastatic melanoma.
  
  
  METHODS
  Patients with metastatic melanoma were randomized to receive Bev (15 mg/kg intravenously every 2 weeks) with or without low-dose IFN-alpha2b (1 MU/m2 subcutaneously daily). Patients exhibiting a clinical response or stable disease after 12 weeks were treated until disease progression.
  
  
  RESULTS
  Thirty-two patients (16 per arm) were accrued (18 male, 14 female; mean age 57.5 years). Both regimens were well tolerated. Six patients developed easily managed exacerbations of preexisting hypertension. Two patients developed grade 3 proteinuria that resolved after a treatment break. IFN-alpha2b therapy was associated with grade 1 to 2 constitutional symptoms. Arterial thromboembolic complications were observed in three patients (two mild myocardial infarctions, one transient ischemic attack), all of whom had risk factors. One patient (Bev plus IFN-alpha2b arm) had locally recurrent scalp disease that partially responded to therapy. Eight patients (five Bev, three Bev plus IFN-alpha2b) had prolonged disease stabilization (24 to 146 weeks). Plasma levels of VEGF and FGF did not correlate with any clinical parameter. The patient with the longest period of stable disease had the highest baseline VEGF and FGF.
  
  
  CONCLUSIONS
  Bev was well tolerated at this dose and prolonged disease stabilization was achieved in one-quarter of metastatic melanoma patients. Low-dose IFN-alpha2b did not augment the activity of Bev.
authors.affiliation: Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, N924 Doan Hall, 410 W 10th Avenue, Columbus, Ohio 43210, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Varker
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Biber
authors.forename: Cheryl
authors.initials: C
authors.lastname: Kefauver
authors.forename: Rhonda
authors.initials: R
authors.lastname: Jensen
authors.forename: Amy
authors.initials: A
authors.lastname: Lehman
authors.forename: Donn
authors.initials: D
authors.lastname: Young
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wu
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Lesinski
authors.forename: Kari
authors.initials: K
authors.lastname: Kendra
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walker
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000068258:Bevacizumab