Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study

J Clin Oncol. 1998 May;16(5):1743-51. doi: 10.1200/JCO.1998.16.5.1743.

Abstract

Purpose: To investigate the response rate, time to treatment failure (TTF), overall survival, and toxicity in patients with metastatic melanoma treated with dacarbazine alone, dacarbazine plus interferon (IFN), dacarbazine plus tamoxifen (TMX), or dacarbazine plus IFN plus TMX.

Materials and methods: Two hundred seventy-one patients (258 were eligible) were randomized in a 2 x 2 factorial design to receive one of the above treatments. The trial was designed to detect a 50% improvement in survival with 83% power.

Results: Nine complete (CRs) and 18 partial responses (PRs) were observed in the patients who received treatments that contained IFN compared with four CRs and 18 PRs in the patients who received treatments that did not contain IFN. Five CRs and 20 PRs occurred in patients treated with TMX compared with eight CRs and 16 PRs in those treated without TMX. Response differences were nonsignificant. The overall median TTF was 2.6 months, and the overall median survival was 8.9 months. There was no significant difference in TTF or survival among any of the different treatments. Poor performance status (PS), hepatic metastases, and weight loss were significant adverse prognostic factors. Twenty-three patients had a TTF greater than 20 months, and these durable responses were evenly distributed among the treatment arms. Significantly more severe and life-threatening toxic events occurred with treatments that contained IFN.

Conclusion: Neither IFN, TMX, nor the combination significantly improved the response rate, TTF, or survival when added to dacarbazine, but IFN significantly increased toxicity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Male
  • Melanoma / drug therapy*
  • Melanoma / secondary*
  • Middle Aged
  • Recombinant Proteins
  • Survival Rate
  • Tamoxifen / administration & dosage
  • Tamoxifen / adverse effects
  • Treatment Failure

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Tamoxifen
  • Dacarbazine