PRELIMINARY EXPERIENCE WITH HIGH-DOSE CISPLATIN, REDUCED GLUTATHIONE AND NATURAL INTERFERON-ALPHA IN DACARBAZINE-RESISTANT MALIGNANT-MELANOMA

Aims and background: The incidence of malignant melanoma is rapidly in creasing in many countries, and when this disease has reached advanced stages, standard therapies have little impact. Dacarbazine (DTIC) is the most effective chemotherapeutic agent with an overall response rat e of 20-25%, but durable responses are uncommon. Interesting results w ith the use of cisplatin (CDDP) have been reported in DTIC-resistant m elanoma. Moreover, malignant melanoma is an immunogenic tumor and a po tential target for biological response modifier (BRM) therapies. The a im 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 natura l interferon-alpha (IFN-alpha) in patients with DTIC-resistant metasta tic melanoma. Methods: The treatment schedule included GSH 1,500 mg/m( 2) i.v. and CDDP 40 mg/m(2) i.v. for 4 consecutive days every 3 weeks, with a maximum of 6 courses, and IFN-alpha 3 MIU i.m, 3 times a week, continuative for a maximum of 12 months. Results: Twelve patients wer e enrolled in this phase II trial. Accrual was stopped due to treatmen t-related toxicity. Ten patients were evaluable for response; there we re 2 partial responses, lasting 5+ and 9+ months, respectively, and 2 cases of stable disease, lasting 3+ and 8+ months. None of these patie nts completed the therapeutic program due to treatment-related side ef fects. Conclusions: This regimen seems to be only partially active in DTIC-resistant metastatic melanoma. Hematologic and non-hematologic (n ausea and vomiting, peripheral neurotoxicity, and asthenia) side effec ts are significant and GSH is not effective in limiting CDDP-related n eurotoxicity in pretreated patients. Therefore, there is no indication to employ this regimen as second-line treatment in metastatic melanom a and these disappointing results highlight the urgent need for new th erapeutic approaches.