Nonseminomatous malignant germ cell tumors in children. Multidrug therapy in Stages III and IV.

Thirty-five children with Stage III and IV nonseminomatous malignant germ cell tumors were treated, between June 1, 1977 and December 31, 1982, at Institut Gustave-Roussy, Villejuif, France, and Hospital General de Ninos, Buenos-Aires, Argentina: 11 sacrococcygeal, 12 ovarian, 6 testicular, 5 intrathoracic, and 1 intrabdominal site. All of them had yolk sac component with high level of AFP, seven had also elevated level of HCG. Thirteen patients had primary chemotherapy, 18 received chemotherapy after incomplete surgical excision, and 4 patients with testicular Stage III tumors had chemotherapy immediately following retroperitoneal lymphadenectomy after orchiectomy, because of persistently elevated AFP levels. The chemotherapy regimen for 1 year's duration, repeated every 21 days, and consisted of 6 courses of dactinomycin-Cytoxan (cyclophosphamide) D1 to D5 and vincristine, Adriamycin (doxorubicin) D21, bleomycin D23, and cisplatin D24. Only three patients received complementary radiotherapy. The toxicity of the chemotherapy regimen was severe, but only one death was due to the therapy (pulmonary fibrosis with bleomycin). The number of surviving patients without evidence of disease was 12 of 16 for Stage III and 12 of 19 for Stage IV. The 25-month survival rate was 63% with a follow-up of 11 months to 5.5 years (median, 22 months). This constitutes a dramatic improvement when compared with the survival rate of 21% of 48 similar patients treated at Institut Gustave-Roussy between 1968 and 1977 with surgery, radiotherapy, and chemotherapy (methotrexate, dactinomycin, and Cytoxan).