Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma

Ann Oncol. 2006 Apr;17(4):571-7. doi: 10.1093/annonc/mdl007. Epub 2006 Feb 9.


Background: The addition of cytokines to chemotherapy (CT) has obtained encouraging but contradictory results in metastatic melanoma. In this phase III trial, we compared the effects of CT [cisplatin, vindesine and dacarbazine (CVD)] with those of concurrent biochemotherapy (bioCT) consisting of CVD plus interleukin-2 and interferon-alpha2b.

Patients and methods: A total of 151 untreated metastatic melanoma patients were randomized, 75 on arm A (cisplatin 30 mg/m2 on days 1-3, vindesine 2.5 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 1-3), and 76 on arm B (same CVD scheme plus interferon-alpha2b on days 1-5 and interleukin-2 on days 1-5 and 8-15, both administered subcutaneously), either recycled every 3 weeks. Response was assessed every two cycles.

Results: Ten percent of the patients were alive at a median of 52 months from start of therapy. We observed a response rate (RR) of 21% on arm A versus 33% on arm B; three patients (4%) given bioCT had complete responses (CRs). Median time to progression (TTP) was identical; median overall survival (OS) time was 12 months on arm A and 11 months on arm B.

Conclusions: BioCT is not better than CT alone; the trend in favor of the bioCT in terms of RR did not translate into better TTP or OS. Therefore, bioCT cannot be recommended as standard first-line therapy for metastatic melanoma.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Dacarbazine / administration & dosage
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Recombinant Proteins
  • Vinblastine / administration & dosage


  • Interferon alpha-2
  • Interferon-alpha
  • Interleukin-2
  • Recombinant Proteins
  • Vinblastine
  • Dacarbazine
  • Cisplatin