Escalating dose of continuous infusion combination chemotherapy for refractory neuroblastoma.

Abstract

This trial was undertaken to determine if a continuous infusion format with increased dose-intensity had antitumor activity with tolerable toxicity in patients with advanced neuroblastoma. Forty heavily pretreated patients with refractory or progressive neuroblastoma received continuous infusion doxorubicin, cisplatin, and etoposide along with bolus ifosfamide in a dose-escalation format. A total of 79 courses of chemotherapy were administered at five different dose levels. Fifteen of 35 assessable patients (43%) achieved either a partial response (PR) or complete response (CR), including five patients with a CR, three with a very good PR (VGPR), and seven with a PR. Hematologic toxicity was severe, but reversible, and other toxicities, although significant, were tolerable and much less than that accepted in a bone marrow transplantation (BMT) setting. This investigation illustrates that response is possible even in an extremely poor-prognosis group of patients, and it suggests that such a regimen may be effective if given before disease progression occurs.