Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Clin Cancer Res. 2009 Dec 1;15(23):7361-7. doi: 10.1158/1078-0432.CCR-09-0761. Epub 2009 Nov 17.
To compare the effectiveness, tolerance, and pharmacokinetics of a single dose of pegfilgrastim to daily filgrastim in children and young adults with sarcomas treated with dose-intensive combination chemotherapy.
Patients were randomized to receive a single dose of 100 mcg/kg of pegfilgrastim s.c. or 5 mcg/kg/day of filgrastim s.c., daily until neutrophil recovery after two treatment cycles with vincristine, doxorubicin, and cyclophosphamide (VDC) and two cycles of etoposide and ifosfamide (IE). The duration of severe neutropenia (absolute neutrophil count, < or =500/mcL) during cycles 1 to 4 and cycle duration for all cycles were compared. Pharmacokinetics of pegfilgrastim and filgrastim and CD34+ stem cell mobilization were studied on cycle 1. Growth factor-related toxicity, transfusions, and episodes of fever and neutropenia and infections were collected for cycles 1 to 4.
Thirty-four patients (median age, 20 years; range 3.8-25.8) were enrolled, and 32 completed cycles 1 to 4. The median (range) duration of absolute neutrophil count of <500/mcL was 5.5 (3-8) days for pegfilgrastim and 6 (0-9) days for filgrastim (P = 0.76) after VDC, and 1.5 (0-4) days for pegfilgrastim and 3.75 (0-6.5) days for filgrastim (P = 0.11) after IE. More episodes of febrile neutropenia and documented infections occurred on the filgrastim arm. Serum pegfilgrastim concentrations were highly variable. Pegfilgrastim apparent clearance (11 mL/h/kg) was similar to that reported in adults.
A single dose per cycle of pegfilgrastim was well tolerated and may be as effective as daily filgrastim based on the duration of severe neutropenia and number of episodes of febrile neutropenia and documented infections after dose-intensive treatment with VDC and IE.
比较在接受剂量密集型联合化疗的儿童和青年肉瘤患者中，单次给予培非格司亭 100μg/kg 皮下注射与每日给予非格司亭 5μg/kg 皮下注射的疗效、耐受性和药代动力学。
患者随机接受单次 100μg/kg 培非格司亭皮下注射或每日 5μg/kg 非格司亭皮下注射，直至两个长春新碱、阿霉素和环磷酰胺（VDC）疗程以及两个依托泊苷和异环磷酰胺（IE）疗程中性粒细胞恢复。比较第 1 至 4 周期和所有周期的周期持续时间内严重中性粒细胞减少症（绝对中性粒细胞计数，<或=500/μL）的持续时间。在第 1 周期研究了培非格司亭和非格司亭的药代动力学和 CD34+干细胞动员情况。收集第 1 至 4 周期的生长因子相关毒性、输血以及发热和中性粒细胞减少症发作和感染情况。
共纳入 34 例患者（中位年龄 20 岁；范围 3.8-25.8），32 例患者完成了第 1 至 4 周期。在 VDC 后，培非格司亭组的绝对中性粒细胞计数<500/μL 的中位（范围）持续时间为 5.5（3-8）天，而非格司亭组为 6（0-9）天（P=0.76）；在 IE 后，培非格司亭组的中位（范围）持续时间为 1.5（0-4）天，而非格司亭组为 3.75（0-6.5）天（P=0.11）。非格司亭组发热性中性粒细胞减少症和记录的感染次数更多。血清培非格司亭浓度高度可变。培非格司亭表观清除率（11 mL/h/kg）与成人报告的清除率相似。
在接受 VDC 和 IE 剂量密集治疗后，与每日非格司亭相比，培非格司亭每周期单次给药在严重中性粒细胞减少症持续时间和发热性中性粒细胞减少症和记录的感染次数方面具有相似的疗效，且耐受性良好。
