Decreased risk of radiation-associated second malignant neoplasms in actinomycin-D-treated patients.

One hundred two long-term survivors of childhood cancers with second malignant neoplasms (SMNs) were collected from 10 institutions. Forty-seven cases fulfilling study criteria were studied to determine the risk of developing a SMN in irradiated fields after exposure to various chemotherapeutic agents. The case control method was used. The risk of developing such tumors was decreased by a factor of 7 in patients receiving actinomycin-D (AMD). The "protective" effect of AMD was more pronounced in patients receiving repeated courses of the agent. No change in relative risk was found for children given antifolates, the vinca alkaloids, or alkylating agents. AMD "protection" is an unexpected finding because the agent is an oncogen in animals and an enhancer of radiation, the latter being a known carcinogen. Possible mechanisms, which remain speculative, are discussed. These results indicate the need for careful long-term observation of cancer survivors to gain understanding of the late effects of multimodal treatments.