Therapy-related malignancies following treatment of germ cell cancer

Given the young age at which testicular cancer is treated and the excellent prognosis for patients suffering from this disease, therapy-related malign ancies represent: a significant problem. Therapy-related solid tumors are a ssociated mainly with the use of radiation therapy, The risk for developing a therapy-related solid tumor is approximately 2- to 3-fold increased comp ared with the general population. Therapy-related leukemias are associated predominantly with chemotherapy, particularly with the use topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia is low, it is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative doses l ess than or equal to 2 g/m(2) and >2 g/m(2), respectively, High cumulative doses of etoposide given over a short: period of time appear to be less leu kemogenic than a similar dose of etoposide given over a longer period of ti me, There might, additionally, be a synergistic effect of cisplatin and eto poside on the induction of therapy-related leukemia. For patients who recei ve high-dose chemotherapy with autologous stem-cell support, the risk of th erapy-related myelodysplastic syndrome and leukemia appears to be substanti ally lower compared with that reported in non-Hodgkin's lymphoma patients u ndergoing high-dose chemotherapy, The transplantation procedure itself does not appear to add to the therapy-related leukemia risk. The risk-benefit a nalysis in patients with testicular cancer clearly favors the use of curren t treatment: regimens including high-dose chemotherapy. However, even the a cceptably low number of therapy-related leukemias should encourage the sear ch for equally effective but less toxic therapies. 1999 Wiley-Liss, Inc.