Preliminary experience with high-dose cisplatin, reduced glutathione and natural interferon-α in dacarbazine-resistant malignant melanoma

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Abstract

Aims and background: The incidence of malignant melanoma is rapidly increasing in many countries, and when this disease has reached advanced stages standard therapies have little impact. Decarbazine (DTIC) is the most effective chemotherapeutic agent with an overall response rate of 20-25%, but durable responses are uncommon. Interesting results with the use of cisplatin (CDDP) have been reported in DTIC-resistant melanoma. Moreover, malignant melanoma is an immunogenic tumor and a potential target for biological response modifier (BRM) therapies. The aim of the present study was to evaluate the efficacy and tolerability of a chemo-immunotherapeutic regimen including high-dose CDDP-combined with glutathione (GSH) to limit platinum- related toxicity, and natural interferon-α (IFN-α) in patients with DTIC- resistant metastatic melanoma. Methods: The treatment schedule included GSH 1,500 mg/m2 i.v. and CDDP 40 mg/m2 i.v. for 4 consecutive days every 3 weeks, with a maximum of 6 courses, and IFN-α 3 MIU i.m. 3 times a week, continuative for a maximum of 12 months. Results: Twelve patients were enrolled in this phase II trial. Accrual was stopped due to treatment- related toxicity. Ten patients were evaluable for response; there were 2 partial responses lasting 6+ and 9+ months, respectively, and 2 cases of stable classes, lasting 3+ and 8+ months. None of these patients completed the therapeutic program due to treatment-related side effects. Conclusions: This regimen seems to be only partially active in DTIC-resistant metastatic melanoma. Hematologic and non-hematologic (nausea and vomiting, peripheral neurotoxicity, and asthenia) side effects are significant and GSH is not effective in limiting CDDP-related neurotoxicity in pretreated patients. Therefore, there is no indication to employ this regimen as second-line treatment. In metastatic melanoma and these disappointing result highlight the urgent need for new therapeutic approaches.

Original languageEnglish
Pages (from-to)48-51
Number of pages4
JournalTumori
Volume84
Issue number1
Publication statusPublished - Jan 1998

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Keywords

  • Cisplatin
  • Glatathione
  • Interferon-α
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research

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