title: Interleukin-2-based biochemotherapy for patients with stage IV melanoma: long-term survivors outside a clinical trial setting.
abstract: BACKGROUND
  The role of Interleukin-2 (IL-2)-based biochemotherapy (BCT) for patients with metastatic melanoma remains controversial and few data of patients treated outside a specialized trial setting are available.
  
  
  METHODS
  Sixty-six consecutive patients treated with BCT for stage IV melanoma were analyzed retrospectively. All patients received BCT consisting of dacarbazine, cisplatin and vinblastine (CVD), interferon alfa-2a (IFN), and IL-2. IL-2 was administered at two different dose levels: 3 x 10(6) U/m(2)/day (BCT-3) and 9 x 10(6) U/m(2)/day (BCT-9), each intravenously on 4 consecutive days (days 5-8, 17-20, 26-29).
  
  
  RESULTS
  Nine of 66 patients achieved a complete (CR) and 11 patients a partial response (PR), resulting in an overall response rate of 30%. Five responses (2 CR and 3 PR) were observed in the 29 patients treated according to the BCT-3 protocol, 15 responses (7 CR and 8 PR) in the 37 patients treated according to the more IL-2 dose-intense BCT-9 protocol (17 vs. 41%; p = 0.033). Median overall survival (OS) for all 66 patients was 10 (range 3-119+) months. Responders had a superior OS than nonresponders (14 vs. 7 months, p < 0.001). After a median follow-up of 70 months, 5 patients are alive. Among them, 4 are in stable CR at 30+, 48+, 79+ and 119+ months, respectively, amounting to a disease-free survival rate of 6% (4/66).
  
  
  CONCLUSIONS
  Long-term disease-free survival for patients with stage IV melanoma can be achieved with BCT outside a highly specialized clinical trial setting. Better selection criteria are needed in order to avoid the unnecessary toxic treatment of the majority of patients.
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Viviane
authors.initials: V
authors.lastname: Hess
authors.forename: Richard
authors.initials: R
authors.lastname: Herrmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Michael
authors.initials: M
authors.lastname: Schwabe
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin