Second cancers following antineoplastic therapy

The occurrence of metachronous malignancies has long been a phenomenon of interest to physicians. The problem of treatment-related malignancies has added to that interest and has contributed to the understanding of carcinogenesis. Prolonged survival of patients with previously lethal diseases is now allowing the expression of long-term toxicities of the intensive therapies being used in many disease settings. Although the oncogenic potential of the various alkylating agents may not be equivalent, they have all been implicated as causing cancer in man. Procarbazine also appears to be highly carcinogenic in man. The intensity of treatment (duration and total dose) is a significant factor in the carcinogenesis of these agents. The dose-response relationship between radiation and cancer induction is less clear, but most believe that increasing radiation exposure increases the risk of cancer in a linear fashion. The combination of intensive chemotherapy and intensive radiotherapy yields the greatest risk for treatment-related hematologic and solid malignancies. To replace effective therapy with less carcinogenic therapy of unproved effectiveness would be difficult since survival curves have not been significantly affected by the evolution of treatment-related cancers. Whether that will hold true for the adjuvant use of intensive therapy remains to be seen. Where feasible, the design of such adjuvant trials should keep the dose-response relationship in mind. If the virtual absence of metachronous leukemia in Hodgkin's disease patients treated with ABVD holds true over time, the search for noncarcinogenic combination therapy will be well worth the effort. Therapeutic options in cancer treatment currently are few, and the benefits of potentially carcinogenic chemotherapy and radiotherapy continue to outweigh the risks.