Carcinogenicity of nitrosoureas in humans

Literature on secondary tumours developing after cancer chemotherapy with nitrosoureas is reviewed. Many case studies show that combination treatments including BCNU and CCNU give rise predominantly to acute leukaemia within an average latent period of about 40 months. However, because other, potentially carcinogenic alkylating agents may be administered during treatment, no direct causal association with nitrosoureas can be made on the basis of these studies. A large case-control study by Boice et al. (1983), however, provides strong evidence of a causal relationship between the induction of acute nonlymphocytic leukaemia (ANLL) and treatment with methyl-CCNU. Among 2067 patients treated with methyl-CCNU and 5-fluorouracil as adjuvant chemotherapy after surgery for gastrointestinal cancers, nine cases of ANLL were observed, whereas 0.71 were expected; the relative risk was 15.9. The results are discussed and are interpreted as providing evidence for the carcinogenicity of methyl-CCNU to humans. They are therefore consistent with other epidemiological data on the carcinogenicity of N-nitroso compounds to man.