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

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...

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Hauptverfasser: Keilholz, Ulrich (VerfasserIn) , Scheibenbogen, Carmen (VerfasserIn) , Möhler, Thomas (VerfasserIn) , Brossart, Peter (VerfasserIn) , Maclachlan, David (VerfasserIn) , Geueke, A.-M. (VerfasserIn) , Jochim, Anita (VerfasserIn) , Hunstein, Werner (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: August 1995
In: Melanoma research
Year: 1995, Jahrgang: 5, Heft: 4, Pages: 283-288
ISSN:1473-5636
DOI:10.1097/00008390-199508000-00013
Online-Zugang:Verlag: https://dx.doi.org/10.1097/00008390-199508000-00013
Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/melanomaresearch/abstract/1995/08000/addition_of_dacarbazine_or_cisplatin_to.13.aspx
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Verfasserangaben:U. Keilholz, C. Scheibenbogen, T. Möhler, P. Brossart, D. Maclachlan, A.-M. Geueke, A. Jochim, W. Hunstein

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520 |a 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-a (IFN-α) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-α/IL-2 alone were studied. Six received DTIC and IFN-α/IL-2, and six received CDDP and IFN-a/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-α/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-α/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-a/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy. 
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