Forty-seven children or adolescents with initial stage IV (42 patients) or stage III (five) advanced neuroblastoma (12 were progressing after relapse and 35 had never reached complete remission [CR] after conventional therapy) were included in a phase II study of the combination of high-dose VP-16 (100 mg/m 2 /d x 5) and high-dose cisplatin (CDDP) (40 mg/m 2 /d x 5). Twenty patients had received prior CDDP therapy (total dose, 100 to 640 mg/m2; median, 320 mg/m 2 ) and 38 of 47 had bone marrow involvement when included in the study. The overall response rate was 55%, with 22% CR. Duration of response was 5 to 18 months, with a median of 10 months. Eight patients are still disease free, with a median observation time of 13 months, but all had received additional therapy after two courses of this regimen. Gastrointestinal toxicity was frequent but tolerable. Myelosuppression was severe but of brief duration, ie, nadir of neutro-STAGE IV neuroblastoma in children over 1 year of age remains one of the major therapeutic challenges in pediatric oncology. Despite advances in conventional regimens 1 -6 and the recent introduction of high-dose chemoradiotherapy with bone marrow rescue, the long-term outcome remains disappointing.' 7 , While the latter approach has produced encouraging results in patients who have achieved complete remission (CR) phase II pilot studies conducted by our group revealed an impressive response rate to a dose of 200 mg/m 2 CDDP in children with relapsed disease who had been previously treated with multiple drug schemata, including CDDP 60 to 100 mg/m2.' 3 VM-26 was shown to be an active agent in phase II studies and although similar data with etoposide (VP-16) are limited, this agent actually shows a comparable activity.14-17 Its value has been shown when combined with low-dose CDDP.' 4 The main advantage over VM-26 is its better tolerance; allergic reactions to VM-26 occur in a high percentage of children with neuroblastoma. 4 The combination of VP-16 and