Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group

J Clin Oncol. 2014 Nov 20;32(33):3771-8. doi: 10.1200/JCO.2013.53.1590. Epub 2014 Oct 20.

Abstract

Purpose: High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective.

Patients and methods: S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS).

Results: In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms.

Conclusion: Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.

Trial registration: ClinicalTrials.gov NCT00006237.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Interferons / administration & dosage
  • Interferons / adverse effects
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Middle Aged
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00006237

Grants and funding