Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects

Melanoma Res. 1995 Aug;5(4):283-7. doi: 10.1097/00008390-199508000-00013.


The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.

Publication types

  • Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cytokines / blood
  • Dacarbazine / administration & dosage
  • Humans
  • Immunotherapy
  • Interferon Type I / administration & dosage
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacokinetics
  • Interleukin-2 / toxicity
  • Melanoma / blood
  • Melanoma / drug therapy*
  • Melanoma / secondary
  • Pilot Projects
  • Recombinant Proteins


  • Adjuvants, Immunologic
  • Cytokines
  • Interferon Type I
  • Interleukin-2
  • Recombinant Proteins
  • Dacarbazine
  • Cisplatin