BEP/VIP IN CHILDREN AND ADOLESCENTS WITH MALIGNANT NONTESTICULAR GERM-CELL TUMORS - COMPARISON OF RESULTS OF MAKEI 83/86, 89 AND 89 PILOT-STUDIES

The treatment regimen of the ongoing cooperative study for non testicular germ cell tumors (MAKEI 89 of the German Society of Pediatric Oncology and Hematology), was stratified as in MAKEI 83 and 86 according to histology, localisation and stage. In the 1989 study, vinblastine was replaced by etoposide, resulting in a chemotherapeutic regimen of 3 to 4 courses BEP and 3 to 4 courses VIP in patients with stage I to IV. Total chemotherapy was reduced for 25%. In children under 1 year of age, bleomycin was omitted and bleomycin dose was reduced to 50%. In children up to 2 years because of two toxic deaths due to bleomycin who were registered in MAKEI 89 Pilot phase. Until Jan. 31, 1993, 230 patients were registered in the MAKEI 89 pilot study and the MAKEI 89 study, containing 186 protocol and 44 follow-up patients (patients with intracranial tumors are excluded for the review). 78 of the registered patients had a teratoma, 9 of these 78 patients suffered from a relapse. In 7 of 9 patients a lasting second remission has been achieved. 12 patients offered with germinoma. 1 of 12 patients had a recurrence but is in second remission. 47 patients had malignant non germinomatous germ cell tumors with an event free survival of 91+/-0.4%. 2 of the 47 patients relapsed and died. Toxicity was mainly hematologic without evidence of long term effects. Bleomycin induced pulmotoxicity (WHO grade IV) was documented in 1 protocol patient (see above). Nephrotoxicity with a grade III (WHO) decrease of creatinine clearance was found in 25% of the documented patients with a fast return to normal values after the end of therapy in most of the children. For the follow-up MAKEI 93 study, different topics are defined. 1. The value of chemotherapy for immature teratoma has to be discussed. 2. In invasive immature teratoma in children over 1 year of age, the effectiveness of chemotherapy should be proved. 3. Germinomas show high platinum sensitivity, therefore a platinum based chemotherapy has to be examined for this risk group. 4. The value of a wait and see strategy similar to the proved regimen in the French germ cell tumor protocol has to be verified in patients with stage I non germinomatous germ cell tumors. 5. An intensification of chemotherapy in patients with malignant stage III and IV non germinomatous germ cell tumors has to be examined as a new therapeutic approach for this risk group.