Toxicity in long-term survivors after adriamycin containing chemotherapy of malignant germ-cell tumors.

In order to assess overall treatment-induced long-term morbidity after high-dose adriamycin-based chemotherapy +/- radiotherapy, clinically significant toxicity was studied in survivors after treatment of advanced germ-cell cancer who had received adriamycin-containing chemotherapy before cisplatin became available in Norway. Most of the patients were also irradiated. The study comprises 47 patients with advanced germ-cell cancer who survived for at least 5 years after chemotherapy containing adriamycin (VACAM: vincristine, adriamycin, cyclophosphamide, actinomycin-D and medroxyprogesterone acetate) as part of their primary systemic treatment (before 1978) or as maintenance chemotherapy after initial cisplatin-based cytotoxic treatment (after 1978). Thirty-two patients also had radiotherapy. The median follow-up was 12.3 years. Forty-one events of late toxicities were recorded in 25 patients, 37 of these were observed after combined radiotherapy and chemotherapy. The most frequent late side effects were cardiotoxicity, gastrointestinal toxicity and neurological disorders observed in 7, 12 and 8 patients, respectively. Three patients who were irradiated to the cardiac region, died of heart failure. Secondary solid cancer developed in 7 patients after a median follow-up of 10.5 years (relative risk 4.8, 95% confidence interval 1.9 to 9.9). In a historical perspective high-dose adriamycin-containing combination chemotherapy if applied with cyclophosphamide and/or radiotherapy, may occasionally be curative in selected patients with advanced germ cell tumours, but leads to an unacceptable high incidence of severe cardiac, gastrointestinal and neurological late side effects. The present follow-up study highlights that such treatment should be avoided in the curatively intended treatment of cancer patients and emphasizes the need of long-term follow-up studies in surviving cancer patients.