Shea T C, Mason J R, Storniolo A M, Newton B, Breslin M, Mullen M, Ward D M, Miller L, Christian M, Taetle R
Department of Medicine, University of California, San Diego.
J Clin Oncol. 1992 Mar;10(3):464-73. doi: 10.1200/JCO.1992.10.3.464.
The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy.
Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B).
The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission.
This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.
本试验旨在研究给予粒细胞巨噬细胞集落刺激因子（GM-CSF）联合或不联合外周血祖细胞（PBPC）对多周期高剂量卡铂化疗所致血液学和非血液学毒性的影响。
18例患有各种实体瘤的患者共接受了40个周期的卡铂治疗，每个周期剂量为1200mg/m²，通过96小时持续输注给药。所有40个疗程均每日静脉输注（IV）4小时，剂量为5或10μg/kg/d的重组人源大肠杆菌衍生的GM-CSF。前20个疗程在无PBPC支持的情况下给药（治疗A）。由于严重的中性粒细胞减少和血小板减少，接下来的20个疗程在给予GM-CSF、PBPC及口服抗生素预防的情况下给药（治疗B）。
添加PBPC支持导致每个周期中性粒细胞减少持续时间（10.5天对7.5天；P = 0.027）、血小板减少持续时间（12.4天对5.2天；P = 0.001）、红细胞输注次数（6次对3次；P = 0.01）和血小板输注次数（10.3次对3.7次；P = 0.013）、住院天数（12.6天对2.9天；P = 0.01）以及静脉使用抗生素天数（11.8天对2.4天；P = 0.007）均显著减少。治疗B组还观察到卡铂的每周剂量强度（206mg/m²/周对285mg/m²/周；P = 0.014）和总剂量（2287mg/m²对3600mg/m²；P = 0.018）显著增加。本研究的总体缓解率为70%，16例可评估患者中有11例实现完全缓解（3例患者）或部分缓解（8例患者）。
GM-CSF与PBPC输注的这种联合是进行多周期高剂量卡铂化疗的有效方法，可能成为未来试验中高剂量化疗给药的模型。
