STUDIES OF DRUG-INDUCED CANCER AND MULTIPLE PRIMARY CANCERS

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Studies of the late effects of drug therapy are conducted, with special emphasis on the carcinogenic potential of drugs used in a therapeutic setting. Studies of cancer chemotherapeutic agents are a logical extension to the Branch's activities involving second cancer following radiation for a first primary, since many cancer patients are exposed to both treatment modalities. Occasionally, opportunities arise to study other drugs of special interest unrelated to treatment. Sources of populations have included cancer patients reported to population-based cancer registries (particularly the Surveillance, Epidemiologic, and End Results program), randomized clinical trials, and persons treated at major institutions. Additional details on collaborative projects can be found in Project No. Z01CPO4412-14 EEB, "Carcinogenic Effects of Therapeutic Drugs" and Project No. Z01CPO4410-14 EEB, "Studies of Persons at High Risk of Cancer." Breast cancer patients treated with chemotherapy were found to have an 11-fold risk of acute non-lymphocytic leukemia, with the risk highest in those treated with melphalan-containing regimens. Long-term survivors who received chemotherapy for non-Hodgkin's lymphoma have an especially high risk of developing a second primary cancer of the bladder, which is likely related to therapy with the known bladder carcinogen cyclophosphamide. Commonly used anticonvulsive drugs to treat epilepsy were not found to increase the overall risk of cancer, although slight increases in lung cancer and non-Hodgkin's lymphoma were noted. Offspring of epileptic patients exposed to anti-convulsive drugs were not at increased risk of childhood cancer. Radiotherapy for cervical cancer significantly reduced the risk of breast cancer due to ovarian ablation. Thorotrast given for cerebral radiography significantly increased the risk of liver cancer and leukemia.