This report is the result of a n Eastern Cooperative Oncology Group (ECOG) study. Four hundred and 15 patients with inoperable metastatic malignant melanoma, excluding those with cutaneous metastases only, were randomized to one of three drug treatments: DTIC alone, methyl-CCNU alone, or the combination DTIC plus methyl-CCNU. Responses were seen in 14% of DTIC patients (19/127), 15% of methyl-CCNU patients (18/119) and 14% of DTIC plus methyl-CCNU patients (18/122). Duration of response was the same (14 weeks) for all three treatment groups. There was no difference among the treatments in achieving complete responses. Survival was improved significantly for responders (50 weeks) compared with nonresponders (15 weeks) regardless of treatment regimen. Toxicities were generally tolerable. DTIC caused significantly more gastrointestinal toxicity than methyl-CCNU. Methyl-CCNU caused significantly more bone marrow toxicity than DTIC. There were three drug-related deaths. All occurred in patients on combination DTIC plus methyl-CCNU. Important pretreatment characteristics that favor response are ambulatory status, female, less than 50 years old, no prior chemotherapy and no liver o r brain metastases. Patients with favorable characteristics combinations had a 30% response rate, while those with unfavorable characteristic combinations had only a 9% response rate.
In a prospective randomized study of 155 patients, dimethyltriazeno imidazole carboxamide, 2.0 or 4.5 mg. per kilogram given for 10 successive daily intravenous doses, resulted in ob;ective response in 28 per cent of 115 evaluable patients. The 2.0 mg. schedule produced a significantly greater rate and duration of response (p S; 0.05) than did the 4.5 mg. schedule. In half of the responding patients the response exceeded 6 months in duration. Urinary melanogens, detected by a qualitative test in 29 per cent of patients tested, suggested widespread disease but were not helpful in diagnosing clinically occult recurrent disease. Toxicity was somewhat greater on the 4.5 mg. regimen, but in general it was mild; there were no drug deaths. The drug, which has some interesting and unusual dose-toxicity-response relationships, appears to be the most effective chemotherapeutic agent for treatment of malignant melanoma.
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