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 testicu lar germ cell tumors (MAKEI 89 of the German Society of Pediatric Onco logy and Hematology), was stratified as in MAKEI 83 and 86 according t o histology, localisation and stage. In the 1989 study, vinblastine wa s 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 c hildren 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 pat ients were registered in the MAKEI 89 pilot study and the MAKEI 89 stu dy, containing 186 protocol and 44 follow-up patients (patients with i ntracranial tumors are excluded for the review). 78 of the registered patients had a teratoma, 9 of these 78 patients suffered from a relaps e. In 7 of 9 patients a lasting second remission has been achieved. 12 patients offered with germinoma. 1 of 12 patients had a recurrence bu t 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 e vidence of long term effects. Bleomycin induced pulmotoxicity (WHO gra de IV) was documented in 1 protocol patient (see above). Nephrotoxicit y with a grade III (WHO) decrease of creatinine clearance was found in 25% of the documented patients with a fast return to normal values af ter the end of therapy in most of the children. For the follow-up MAKE I 93 study, different topics are defined. 1. The value of chemotherapy for immature teratoma has to be discussed. 2. In invasive immature te ratoma in children over 1 year of age, the effectiveness of chemothera py should be proved. 3. Germinomas show high platinum sensitivity, the refore 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 r egimen in the French germ cell tumor protocol has to be verified in pa tients with stage I non germinomatous germ cell tumors. 5. An intensif ication of chemotherapy in patients with malignant stage III and IV no n germinomatous germ cell tumors has to be examined as a new therapeut ic approach for this risk group.