St Anna Children's Hospital, Kinderspitalgasse 6, Vienna, Austria.
J Clin Oncol. 2010 Jul 20;28(21):3516-24. doi: 10.1200/JCO.2009.27.3524. Epub 2010 Jun 21.
To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim).
From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 microg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled.
The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest.
Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.
减少快速 COJEC（顺铂、长春新碱、卡铂、依托泊苷和环磷酰胺的快速给药方案）诱导期间发热性中性粒细胞减少症的发生。在高危神经母细胞瘤-1（HR-NBL1）试验中，国际儿科肿瘤学会欧洲神经母细胞瘤组（SIOPEN）将患者随机分配至预防性（PP）与症状触发粒细胞集落刺激因子（GCSF；非格司亭）。
从 2002 年 5 月至 2005 年 11 月，16 个国家的 239 名患者被随机分配接受或不接受 PPGCSF。其中 144 名男孩，中位年龄为 3.1 岁（范围，1 至 17 岁），其中 217 名患有国际神经母细胞瘤分期系统（INSS）第 4 期，22 名患有第 2 或 3 期 MYCN 扩增疾病。预防性组在每 8 个 COJEC 化疗周期后接受一次 5 mcg/kg GCSF 的每日单剂量治疗，并在下次周期前 24 小时停止治疗。无论血液学恢复如何，只要感染得到控制，每 10 天给予一次化疗。
PPGCSF 组发热性中性粒细胞减少症发作次数明显减少（P =.002），发热天数（P =.004）、住院天数（P =.017）和抗生素天数（P =.001）。报告的常见毒性标准（CTC）分级毒性也显著降低：每周期感染（P =.002）、发热（P <.001）、严重白细胞减少症（P <.001）、中性粒细胞减少症（P <.001）、粘膜炎（P =.002）、恶心/呕吐（P =.045）和便秘（P =.008）。严重体重减轻减少了 50%，差异有统计学意义（P =.013）。PPGCSF 组完成方案的时间明显缩短，表明对快速诱导方案的依从性也显著提高（P =.005）。PPGCSF 并未对反应率或外周血干细胞采集的成功率产生不利影响。
根据这些结果，建议所有接受快速 COJEC 诱导的患者使用预防性 GCSF。
