AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE-2 STUDY OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (FILGRASTIM) AS AN ADJUNCT TO COMBINATION CHEMOTHERAPY IN PEDIATRIC-PATIENTS WITH METASTATIC NEUROBLASTOMA

Administration of combination chemotherapy to children with metastatic neuroblastoma induces profound myelosuppression resulting in chemothe rapy treatment delays and febrile neutropenic episodes. The objective of this randomised multicentre study was to assess the incidence, dura tion and severity of neutropenia when filgrastim is added to induction chemotherapy administered to patients with metastatic neuroblastoma. In this study, 59 patients with metastatic neuroblastoma were randomis ed to receive chemotherapy (control group, n = 28) or chemotherapy plu s filgrastim (filgrastim group, n = 31). Chemotherapy consisted of fou r cycles of cyclophosphamide, vincristine and doxorubicin (CADO) alter nating at 21-day intervals with cisplatin and etoposide (CDDP-VP16). F ilgrastim was administered subcutaneously at a dose of 5 mu g/kg/day f rom day 7 for up to 14 days. The incidence of neutropenia (absolute ne utrophil count [ANC] < 0.5 x 10(9)/l) in the filgrastim group was not reduced after the first CADO course. However, significant reductions w ere observed after courses 2, 3 and 4. The duration of neutropenia and of intravenous antibiotic use were significantly reduced in the filgr astim group over the whole study period (9 days versus 26 days, P < 0. 001; 12 days versus 20 days, P = 0.04, respectively). However, the dur ation of hospitalisation and the incidence of febrile neutropenia were not significantly reduced. Compliance to treatment was good and the a bility to administer chemotherapy without treatment delays was signifi cantly better in the filgrastim group (P < 0.05). Event-free survival was greater in the filgrastim than in the control group (2.4 years ver sus 1.3 years; P = 0.072). Filgrastim is a beneficial adjunct to combi nation induction chemotherapy used in the treatment of metastatic neur oblastoma. (C) 1998 Elsevier Science Ltd. All rights reserved.