title: Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma.
abstract: OBJECTIVE
  Biochemotherapy improves responses in metastatic melanoma, but not overall survival, in randomized trials. We developed a maintenance biotherapy regimen after induction biochemotherapy in an attempt to improve durability of responses and overall survival.
  
  
  METHODS
  One hundred thirty-three chemotherapy-naïve patients with metastatic melanoma without CNS metastases were treated at 10 melanoma centers. The biochemotherapy induction regimen included cisplatin, vinblastine, dacarbazine, decrescendo interleukin-2 (IL-2), and interferon alfa-2b with granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine support. Patients not experiencing disease progression were eligible for maintenance biotherapy with low-dose IL-2 and GM-CSF followed by intermittent pulses of decrescendo IL-2 over 12 months. Patients were observed for response, progression-free survival, toxicity, and overall survival.
  
  
  RESULTS
  The response rate to induction biochemotherapy was 44% (95% CI, 35% to 52%; complete response, 8%; partial response, 36%; stable disease, 29%). The median number of biochemotherapy cycles was four, and the median number of maintenance biotherapy cycles was five. The median progression-free survival was 9 months, and the median survival was 13.5 months. The 12-month and 24-month survival rates were 57% and 23%, respectively. Twenty percent of patients remain alive (12 without disease), with median follow-up of 30 months (95% CI, 25+ to 45+ months). Thirty-nine percent of patients developed CNS metastases. The median times to CNS progression and death were 8 months and 5 months, respectively.
  
  
  CONCLUSIONS
  Maintenance biotherapy after induction biochemotherapy seems to prolong progression-free survival and improve overall survival compared with recent multicenter trials of biochemotherapy or chemotherapy. The regimen should be studied in a randomized clinical trial in patients with advanced metastatic melanoma. CNS progression remains a formidable challenge.
authors.affiliation: Melanoma Program, The Angeles Clinic and Research Institute, 2001 Santa Monica Blvd, Suite 560 W, Santa Monica, CA 90404, USA. soday@theangelesclinic.org
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'Day
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Peter
authors.initials: P
authors.lastname: Boasberg
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: Clay M
authors.initials: CM
authors.lastname: Anderson
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.forename: Thomas
authors.initials: T
authors.lastname: Amatruda
authors.forename: Evan M
authors.initials: EM
authors.lastname: Hersh
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D014747:Vinblastine; D003606:Dacarbazine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin