Preliminary experience with high-dose cisplatin, reduced glutathione and natural interferon-alpha in dacarbazine-resistant malignant melanoma.
OBJECTIVE
The incidence of malignant melanoma is rapidly increasing 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 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 natura interferon-alpha (IFN-alpha) 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-alpha 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 5+ and 9+ months, respectively, and 2 cases of stable disease, 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 results highlight the urgent need for new therapeutic approaches.
Bajetta
E
E
Division of Medical Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Rimassa
L
L
Carnaghi
C
C
Del Vecchio
M
M
Celio
L
L
Cassata
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000008:administration & dosage; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D003606:Dacarbazine; D005978:Glutathione; D002945:Cisplatin