Initial clinical trials with methyl-ccnu 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (meccnu)

Fifty patients have been treated with MeCCNU, 26 of whom received multiple doses at 6-week intervals. The primary toxicity of this agent is delayed myelosuppression, which appears 3 to 5 weeks after a single oral dose and is usually manifest as thrombocytopenia. No significant renal or hepatic side effects have been observed. Some evidence for cumulative marrow toxicity was noted in 42% of the patients receiving multiple doses. In previously treated patients there is usually consistent, but tolerable, marrow suppression at a dose of 220 mg/m2 although extent of prior therapy will necessitate individualizing the dose in many instances. Patients without prior therapy tolerated 220 mg/m2, but doses of 290 mg/m2 were usually accompanied by considerable toxicity especially with subsequent courses. Preliminary clinical trials indicate that MeCCNU is well tolerated and biologically active when given orally at these doses. Ten of the 50 patients in the study had objective therapeutic responses to MeCCNU. Responses were seen in patients with melanoma, primary brain tumors, Hodgkin's disease, lymphosarcoma, and reticulum cell sarcoma.