CARCINOGENIC AND OTHER ADVERSE-EFFECTS OF PROCARBAZINE IN NONHUMAN-PRIMATES

Abstract

The carcinogenic potential of procarbazine is under investigation in 3 species (Macaca mulatta, M. fascicularis and Cercopithecus aethiops) of nonhuman primates. A total of 55 monkeys received procarbazine s.c., p.o. [orally], or i.p. for periods of up to 12 yr. Eleven of the 42 monkeys (26%) necropsied thus far had malignant neoplasms, 6 of which were acute leukemia. Two monkeys developed osteogenic sarcomas, 2 developed hemangiosarcomas and a single case of lymphocytic lymphoma was found. The average total dose of procarbazine received by the monkeys developing cancers was 36.0 g. The average duration of procarbazine treatment was 75 mo. A number of toxic effects of procarbazine seen in humans were also noted in this series of monkeys, including vomiting and myelosuppression. Another striking toxic effect was on the reproductive system of males. The majority of adult males necropsied to date had testicular atrophy with complete aplasia of the germinal epithelium.