Nitrosourea combination chemotherapy: 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (methyl-CCNU) and cyclophosphamide.

MCCNU and cyclophosphamide are synergistic in animal tumor systems and have different chronology patterns for dose-limiting myelosuppression. The combination was employed in 49 patients with metastatic cancer with each drug administered on successive days and repeated at 6-week intervals. A total of 108 courses of therapy were monitored, and leukopenia (WBC less than 3,000 cells/mm3) and thrombocytopenia (platelets less than 150,000/mm3) were observed in 47 and 30%, respectively, at nadir days 15 and 22. No clinically beneficial effects were observed in 40 patients with measurable disease. Combination chemotherapy employing nitrosoureas have not, as in this study, generally demonstrated synergistic therapeutic effects possibly related to the low level of antitumor activity of nitrosoureas in solid tumors and the use of suboptimal doses for one of more agents in the combination.