title: Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects.
abstract: 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.
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D003606:Dacarbazine / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D007370:Interferon Type I / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D010865:Pilot Projects; D011994:Recombinant Proteins
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine; D002945:Cisplatin