McCowage G B, White L, Carpenter P, Lockwood L, Toogood I, Tiedemann K, Shaw P J
Department of Haematology/Oncology, Sydney Children's Hospital, Randwick, Australia.
Med Pediatr Oncol. 1997 Aug;29(2):108-14. doi: 10.1002/(sici)1096-911x(199708)29:2<108::aid-mpo8>3.0.co;2-i.
Combination chemotherapy with vincristine, etoposide, and high-dose, escalating cyclophosphamide (VETOPEC) is an effective regimen in pediatric patients with high-risk solid tumors. The toxicity of the regimen is predominantly haematologic. This study addressed the role of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) following each cycle of chemotherapy in decreasing neutropaenia, incidence of fever/ hospitalization, and/or increasing chemotherapy dose-intensity.
Twenty-nine children with recurrent solid tumors were treated with the VETOPEC regimen. Sequential cohorts of patients received no GM-CSF (Group I), or GM-CSF in a dosage of 5 micrograms/kg/day (Group II) or 10 micrograms/kg/day (Group III) on days 4-18 of each chemotherapy cycle. Up to four cycles of chemotherapy were analysed with respect to haematopoietic recovery, clinical parameters, and dose intensity.
Neutrophil recovery was significantly more rapid in patients treated with GM-CSF. Time to achieving an absolute neutrophil count (ANC) over 0.5 x 10(9)/L in Groups I, II, and III were 21, 18, and 16 days, respectively (P < 0.0001). Time to achieving an absolute neutrophil count (ANC) over 1.0 x 10(9)/L in Groups I, II, and III were 24, 19, and 17 days, respectively (P < 0.0001). There was no significant difference in the incidence of febrile neutropaenia between the three groups. Febrile neutropaenia occurred following 42, 68, and 62% of chemotherapy cycles in Groups I, II, and III, respectively (P = 0.27). Chemotherapy dose intensity was not different between the three groups. GM-CSF was associated with pericarditis and myalgias in one patient, and transient hypoxia/hypotension in another.
GM-CSF led to significantly more rapid neutrophil recovery following VETOPEC chemotherapy, but did not lead to any demonstrable clinical benefit, either in reducing febrile events, or in increasing chemotherapy dose intensity.
长春新碱、依托泊苷及大剂量递增环磷酰胺联合化疗方案（VETOPEC）对高危实体瘤患儿有效。该方案的毒性主要为血液学毒性。本研究探讨在化疗的每个周期后使用重组人粒细胞巨噬细胞集落刺激因子（GM-CSF）在减少中性粒细胞减少、发热/住院发生率及/或增加化疗剂量强度方面的作用。
29例复发性实体瘤患儿接受VETOPEC方案治疗。连续几组患者在每个化疗周期的第4 - 18天不接受GM-CSF（I组），或接受剂量为5微克/千克/天的GM-CSF（II组）或10微克/千克/天的GM-CSF（III组）。对多达四个化疗周期的造血恢复、临床参数及剂量强度进行分析。
接受GM-CSF治疗的患者中性粒细胞恢复明显更快。I组、II组和III组达到绝对中性粒细胞计数（ANC）超过0.5×10⁹/L的时间分别为21天、18天和16天（P < 0.0001）。I组、II组和III组达到绝对中性粒细胞计数（ANC）超过1.0×10⁹/L的时间分别为24天、19天和17天（P < 0.0001）。三组之间发热性中性粒细胞减少的发生率无显著差异。I组、II组和III组分别在42%、68%和62%的化疗周期后发生发热性中性粒细胞减少（P = 0.27）。三组之间化疗剂量强度无差异。GM-CSF与1例患者的心包炎和肌痛以及另1例患者的短暂性缺氧/低血压有关。
GM-CSF使VETOPEC化疗后中性粒细胞恢复明显加快，但在减少发热事件或增加化疗剂量强度方面未带来任何明显的临床益处。
