CA: A Cancer Journal for Clinicians, Vol 32, 258-279, Copyright
© 1982 by American Cancer Society
Cancer Risks of Medical Treatment
David Schottenfeld M.D.1
1 Attending Physician and Chief of the Epidemiology and Preventive Medicine Service in the Department of Medicine, and Director of Cancer Control, of Memorial Sloan-Kettering Cancer Center in New York, New York.
The critical assessment for carcinogenicity of drugs presently in use must be balanced by demonstrable therapeutic benefits. Of approximately 20,000 generically different drug products currently available in the United States, those established as human oncogens are the cytotoxic alkylating agents. immunosuppressive agents, estrogens, oral contraceptives, androgenic anabolic steroids, methoxypsoralen, and phenacetin-containing analgesics. DES. and possibly phenytoin, are the only known examples of human transplacental carcinogens.
The epidemiologic evidence of carcinogenicity for other suspect drugs such as metronidazole (Flagy®). isoniazid, and reserpine is at present either lacking or is conflicting. Of potential significance is the interaction of drugs that are tertiary amines (e.g., aminopyrine, chlorpromazine, methadone, and oxytetracycline) with nitrite in the acid solution of the stomach to form dialkylnitrosamines, which are potent carcinogens in animals. This process of nitrosation may be inhibited by antioxidants such as ascorbic acid or glutathione.
The risk-benefit evaluation of a drug should take into account the likely outcome of the disease if untreated, and whether or not safer alternative therapeutic agents are available. For example, the risks incurred by the use of chlornaphazine or chlorambucil in the treatment of polycythemia vera are considered as excessive as compared with the benefits offered by alternative therapeutic measures. When agents are prescribed that are potentially carcinogenic, but whose continued use by society is viewed as cost-effective, then these should be formulated and prescribed at the lowest dose and for the shortest period of time required to achieve the desired result.
Careful premarketing laboratory and clinical screening and postmarketing epidemiologic surveillance are essential for ensuring safety and efficacy. The clinician has a vital role in detecting previously unsuspected iatrogenic hazards, and in educating the public about the indications, contraindications, and side effects of each therapeutic agent.
