title: Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial.
abstract: OBJECTIVE
  The addition of cytokines to chemotherapy has produced encouraging results in advanced melanoma. In this phase III trial, we compared the effects of chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon alfa-2b.
  
  
  METHODS
  Metastatic melanoma patients who had not previously received chemotherapy were stratified by prognostic factors and given chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was assessed every 6 weeks.
  
  
  RESULTS
  Among 190 patients enrolled, 91 were assessable for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were alive a median of 52 months from start of therapy. Response rates were 48% for biochemotherapy and 25% for chemotherapy (P =.001); six patients given biochemotherapy and two given chemotherapy had complete responses. Median time to progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for chemotherapy (P =.008); median survival was 11.9 and 9.2 months, respectively (P =.06). The influence of treatment on TTP and survival was confirmed in multivariate analyses with other prognostic factors not included in the original stratification. Biochemotherapy produced substantially more constitutional, hemodynamic, and myelosuppressive toxic effects.
  
  
  CONCLUSIONS
  Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.
authors.affiliation: Department Melanoma/Sarcoma, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. oeton@mdanderson.org
authors.forename: Omar
authors.initials: O
authors.lastname: Eton
authors.forename: Sewa S
authors.initials: SS
authors.lastname: Legha
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Buzaid
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hodges
authors.forename: Sigrid E
authors.initials: SE
authors.lastname: Ring
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Papadopoulos
authors.forename: Carl
authors.initials: C
authors.lastname: Plager
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: East
authors.forename: Feng
authors.initials: F
authors.lastname: Zhan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin