Michon J M, Hartmann O, Bouffet E, Meresse V, Coze C, Rubie H, Bordigoni P, Cattiaux E, Ward N, Bernard J L, Lemerle J, Zucker J M, Philip T
Department of Paediatric Oncology, Institut Curie, Paris, France.
Eur J Cancer. 1998 Jun;34(7):1063-9. doi: 10.1016/s0959-8049(98)00061-6.
Administration of combination chemotherapy to children with metastatic neuroblastoma induces profound myelosuppression resulting in chemotherapy treatment delays and febrile neutropenic episodes. The objective of this randomised multicentre study was to assess the incidence, duration 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 randomised to receive chemotherapy (control group, n = 28) or chemotherapy plus filgrastim (filgrastim group, n = 31). Chemotherapy consisted of four cycles of cyclophosphamide, vincristine and doxorubicin (CADO) alternating at 21-day intervals with cisplatin and etoposide (CDDP-VP16). Filgrastim was administered subcutaneously at a dose of 5 micrograms/kg/day from day 7 for up to 14 days. The incidence of neutropenia (absolute neutrophil count [ANC] < 0.5 x 10(9)/l) in the filgrastim group was not reduced after the first CADO course. However, significant reductions were observed after courses 2, 3 and 4. The duration of neutropenia and of intravenous antibiotic use were significantly reduced in the filgrastim 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 duration of hospitalisation and the incidence of febrile neutropenia were not significantly reduced. Compliance to treatment was good and the ability to administer chemotherapy without treatment delays was significantly better in the filgrastim group (P < 0.05). Event-free survival was greater in the filgrastim than in the control group (2.4 years versus 1.3 years; P = 0.072). Filgrastim is a beneficial adjunct to combination induction chemotherapy used in the treatment of metastatic neuroblastoma.
对患有转移性神经母细胞瘤的儿童进行联合化疗会引起严重的骨髓抑制，导致化疗治疗延迟和发热性中性粒细胞减少症发作。这项随机多中心研究的目的是评估在转移性神经母细胞瘤患者的诱导化疗中添加非格司亭时中性粒细胞减少症的发生率、持续时间和严重程度。在本研究中，59例转移性神经母细胞瘤患者被随机分为接受化疗（对照组，n = 28）或化疗加非格司亭（非格司亭组，n = 31）。化疗包括四个周期的环磷酰胺、长春新碱和多柔比星（CADO），每21天交替使用顺铂和依托泊苷（CDDP-VP16）。从第7天起，非格司亭以5微克/千克/天的剂量皮下注射，持续14天。在第一个CADO疗程后，非格司亭组中性粒细胞减少症（绝对中性粒细胞计数[ANC]<0.5×10⁹/升）的发生率并未降低。然而，在第2、3和4个疗程后观察到显著降低。在整个研究期间，非格司亭组中性粒细胞减少症的持续时间和静脉使用抗生素的时间显著缩短（分别为9天对26天，P<0.001；12天对20天，P = 0.04）。然而，住院时间和发热性中性粒细胞减少症的发生率并未显著降低。治疗依从性良好，非格司亭组在不延迟治疗的情况下进行化疗的能力明显更好（P<0.05）。非格司亭组的无事件生存期长于对照组（2.4年对1.3年；P = 0.072）。非格司亭是用于治疗转移性神经母细胞瘤的联合诱导化疗的有益辅助药物。
