Granulocyte-colony stimulating factor and multiple cycles of strongly myelosuppressive alkylator-based combination chemotherapy in children with neuroblastoma

BACKGROUND. The authors assessed key effects of granulocyte-colony stimulat ing factor (G-CSF) used prophylactically with multiple cycles of strongly m yelosuppressive alkylator-based combination chemotherapy. To the authors' k nowledge, no large study has focused on G-CSF in this setting, yet this kin d of treatment has recently become standard for poor risk pediatric solid t umors such as neuroblastoma. PATIENTS AND METHODS. Children with neuroblastoma received cyclophosphamide 140 mg/kg (i.e., 4200 mg/m(2)), doxorubicin 75 mg/m(2), and vincristine (C AV) in cycles 1, 2, 4, and 6 and cisplatin 200 mg/m(2) and etoposide 600 mg /m(2) (P/VP) in cycles 3, 5, and 7. To maximize dose intensity, chemotherap y was begun as soon as the absolute neutrophil count (ANC) was greater than or equal to 500/muL and platelet count was greater than or equal to 100,00 0/muL. No cytokines were used during 1990-1994 (control group; n = 28), but G-CSF was used from 1995 to 1998 (G-CSF group; n = 30) at 5 mug/kg/day sub cutaneously from 1 day after chemotherapy until the ANC was greater than or equal to 500/muL on 2 successive days or was greater than or equal to 1000 /muL. RESULTS, Each cycle of CAV decreased ANCs to < 200/<mu>L in all 58 patients ; recovery to 200/muL and to 500/muL was significantly sooner with G-CSF. I n contrast, P/VP did not invariably cause severe neutropenia: similar numbe rs of patients in each group maintained ANCs greater than or equal to 200/m uL and greater than or equal to 500/muL; recovery to 500/muL (but not to 20 0/muL) was significantly faster in the G-CSF group. G-CSF had no impact on rates of febrile episodes. Bacterial/fungal infections were slightly less f requent in the G-CSF group with CAV (P = 0.11) but not with P/VP. Dose inte nsity through cycle 4 was the same in both groups. Beginning with cycle 3, G-CSF patients had slower recovery to platelet counts greater than or equal to 100,000/muL. Response rates were similar in the two groups. CONCLUSIONS. With multiple cycles of strongly myelosuppressive alkylator-ba sed combination chemotherapy, prophylactic use of G-CSF hastened ANC recove ry but did not reduce the incidence of febrile episodes, had little impact on infection rates, did not yield augmented dose intensity, was associated with prolonged thrombocytopenia, and had no effect on response rates of neu roblastoma. The data support more limited use of G-CSF. (C) 2000 American C ancer Society.