title: ECOG phase II trial of graded-dose peginterferon α-2b in patients with metastatic melanoma overexpressing basic fibroblast growth factor (E2602).
abstract: OBJECTIVE
  We investigated the use of graded-dose peginterferon α-2b (Peg-IFN) in patients with stage IV melanoma overexpressing basic fibroblast growth factor (FGF-2). The primary objective was suppression of plasma FGF-2 to within reference range (≤ 7.5 pg/mL).
  
  
  METHODS
  Plasma FGF-2 was measured at baseline (step 1), and patients with concentrations of 15 pg/mL or more were eligible for study treatment (step 2). Peg-IFN was given weekly at a starting dose of 0.5 μg/kg/wk with increment every 3 weeks based on serial FGF-2 concentrations.
  
  
  RESULTS
  Two hundred seven patients entered step 1; 45 (22%) overexpressed FGF-2 (median = 22 pg/dL). Twenty-nine eligible patients entered step 2 and received treatment. Patients' median age was 64 years (range, 29-84 years). Most had more than two prior therapies. FGF-2 decreased in 28 (97%) patients, with suppression to reference range in 10 (35%). Median time to FGF-2 suppression was 30 days. The best clinical responses were partial response (7%) and stable disease (17%). Median progression-free survival (PFS) and overall survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely than those who did not to have a response or stable disease (P = 0.03). VEGF concentrations decreased in 27 patients (93%) during treatment and paralleled those of FGF-2 over time. We found no compensatory increase in VEGF among those with FGF-2 suppression.
  
  
  CONCLUSIONS
  Graded-dose Peg-IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2. Over one third of patients had complete suppression of plasma FGF-2, which correlated with clinical response to this therapy.
authors.affiliation: Authors' Affiliations: Gundersen Health System; Gundersen Medical Foundation, La Crosse, Wisconsin; Dana-Farber Cancer Institute, Boston, Massachusetts; University of Alabama Comprehensive Cancer Center, Birmingham, Alabama; and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Donghoon
authors.initials: D
authors.lastname: Shin
authors.forename: Steven M
authors.initials: SM
authors.lastname: Callister
authors.forename: Dean A
authors.initials: DA
authors.lastname: Jobe
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Tarhini
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D015870:Gene Expression; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b