The physiologic disposition of radioactive-labelled CCNU and MeCCNU was studied in patients receiving these drugs as part of their early clinical trial. CCNU was given orally in doses of 30-100 mg/m2 a n d MeCCNU in doses of 120-290 mg/m?. With both drugs, significant plasma levels of radioactivity were detected in as early as 10 min. with peak levels occurring a t 1 to 6 hours. Plasma levels of isotope were prolonged, a n d the patterns of decline of radioactivity from plasma were similar for the same labelled moieties of CCNU and MeCCNU. Approximately 60% of the radioactivity given was excreted in the urine within 48 hours and of this more than 50% was excreted in the first 12 hours. Radioactivity was found in the cerebrospinal fluid of patients given both drugs, and, with CCNU, these levels paralleled concurrent plasma levels. T h e degradation of both drugs appears to be extremely rapid since the intact drug could not be detected in any plasma, CSF, or urine sample.
N THE PAST SEVERAL YEARS, THERE HAS BEEN I a considerable interest in a unique group of antitumor agents known as the nitrosoureas. This group includes such clinically useful agents as 1,3 Bis (2-chloroethy1)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU), and most recently 1-(2chloroethyl)-3-(4-methyl cyclohexy1)-1 -nitrosourea (MeCCNU).3,6-8.10,'6.'s.2B Structurally, these drugs are all similar in that they have the basic nitrosourea configuration with the addition of chloroethyl and cyclohexyl groups. CCNU differs from BCNU in the substitution of a cyclohexyl group for one chloroethyl group, and MeCCNU differs from CCNU only in the addition of a methyl group in the four-