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53 patients with intractable malignant diseases that were treated with a new alkylating agent, 4-N, N-bis (2-chloroethyl) amino phenyl N (P-carboxyphenyl) carbamate, also known as ‘IC-140’ were evalua

This report is the result of an 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 or brain metastases. Patients with favorable characteristics combinations had a 30% response rate, while those with unfavorable characteristic combinations had only a 9% response rate.

One hundred twelve evaluable patients with metastatic malignant melanoma were randomized to receive either a combination of DTIC 100 mg/m2/day × 5 days and BCNU 75 mg/m2/day × 2 days or DTIC 150 mg/m2/day × 5 days alone. The combination treatment yielded 12/61 responders as compared with 9/51 with DTIC alone. Responders survived significantly longer (7 months) than did nonresponders (3 months). Toxicity of both treatments was tolerable, but more frequent bone marrow suppression was encountered with DTIC-BCNU combination. Patients were analyzed for relation between survival and the following: regional node dissection, length of the free interval, and positive urinary melanogens. Only the latter relation tended to be positive. We conclude that DTIC is the best agent for the therapy of melanoma with an expected response rate of 20%, and that its combination with BCNU does not add to its therapeutic effectiveness except in patients with central nervous system metastases.

Phenesterin was evaluated in 222 patients with two different dosage regimens, one by daily treatment and the other with an intermittent schedule. Toxicity was moderate with both programs. The largest group of patients treated had breast cancer; they experienced a 10% response rate. Of interest was a higher percentage of responses in ovarian cancer (36%). An expanded study of patients with ovarian cancer would be of interest.