A multicenter phase II clinical trial using dacarbazine and continuous infusion interleukin-2 for metastatic melanoma. Clinical data and immunomonitoring

Cancer. 1995 Feb 15;75(4):1038-44. doi: 10.1002/1097-0142(19950215)75:4<1038::aid-cncr2820750421>3.0.co;2-f.

Abstract

Background: Treatment of patients with metastatic melanoma with either dacarbazine or recombinant interleukin-2 (rIL-2) resulted in a response rate of approximately 15%. This study investigates the possible synergism of this chemoimmunotherapy combination.

Methods: Fifty-seven patients with metastatic malignant melanoma received 135 treatment cycles. Treatment consisted of dacarbazine (Days 1-5) at 250 mg/m2 by a 30-minute slow infusion, and interleukin-2 by constant intravenous infusion (Days 21-25 and 28-32) at 18 x 10(6) IU/m2/24 hours. After this treatment cycle, a 1-week rest was scheduled, and in the absence of undue toxicity or tumor progression, patients received a second cycle as described. Maximum treatment consisted of two induction and four maintenance cycles. In a subgroup of patients, immunoparameters were analyzed to identify prognostic factors. Standard supportive care was given.

Results: Common toxicities included fever, hypotension, nausea/vomiting, anemia, leukopenia, thrombocytopenia, an increase in serum lactic dehydrogenase levels and diarrhea. The objective response rate was 15.8% (one complete response and eight partial responses). In 14 patients, the disease stabilized. For patients who had an objective response, median response duration was 13.9 months (6.3-39.0+), and median survival was 19.0 months (6.3-39.0+); overall survival was 9.3 months (0.8-39.0+). Immunomonitoring did not reveal any relevant prognostic factors for overall response.

Conclusions: Sequential treatment with dacarbazine and rIL-2 is feasible and produces long-lasting responses in a minority of patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Combined Modality Therapy
  • Dacarbazine / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Male
  • Melanoma / mortality
  • Melanoma / secondary*
  • Melanoma / therapy*
  • Middle Aged
  • Prognosis
  • Regression Analysis
  • Remission Induction
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Interleukin-2
  • Dacarbazine