CARBOPLATIN AND VP-16 IN MEDULLOBLASTOMA - A PHASE-II STUDY OF THE FRENCH-SOCIETY-OF-PEDIATRIC-ONCOLOGY (SFOP)

The purpose of this study is to evaluate the antitumor activity of com bination carboplatin and etoposide in measurable medulloblastoma. From January '89 to January '92, 26 patients with medulloblastoma were inc luded in a multicentric phase II study of 2 courses of carboplatin 160 mg/m(2)/d day 1 to day 5 and VP16 100 mg/m(2)/d day 1 to day 5. Media n age was 10 years (19 months-14.5 years). First treatment was surgery alone in 1 patient, surgery + radiotherapy in 4 patients, surgery + c hemotherapy in 2 patients less than 3 years old, surgery + radiotherap y + chemotherapy in 19 patients (''8 drugs in 1 day'' based:17, SIOP I :1, SIOP II:1). Previous treatment included cisplatin (20 cases), carb oplatin (1 case), and VP16 (7 cases). Measurable disease was evaluated by CT scan, MRI or myelogram and CSF. Response rate (RR) was 72 +/- 1 0%:8 complete responses (CR), 10 partial responses (PR), 1 objective e ffect (OE), 6 progressive disease (PD), 1 non-evaluable. Thirty-six co urses were evaluated for toxicity. Median duration of WHO grade 4 neut ropenia was 8 days (O-23). One patient died at day 18 after the first course because of diffuse haemorrhage during septic aplasia. Five othe r non-life-threatening septicemias were recorded. Median number of pla telet transfusions was 1 (0-4). One child who had achieved a PR after two courses died from CNS bleeding after the third course. This drug c ombination achieves a high response rate in childhood medulloblastoma. Severe toxicity has been mainly encountered in previously heavily tre ated patients. Tolerance may be acceptable in newly diagnosed children , but careful hematological follow-up and platelet transfusional suppo rt are definitely mandatory. (C) 1994 Wiley-Liss, Inc.