Fosså S D, Kaye S B, Mead G M, Cullen M, de Wit R, Bodrogi I, van Groeningen C J, De Mulder P H, Stenning S, Lallemand E, De Prijck L, Collette L
Department of Medical Oncology and Radiotherapy, Norwegian Radium Hospital, Oslo.
J Clin Oncol. 1998 Feb;16(2):716-24. doi: 10.1200/JCO.1998.16.2.716.
To determine the effect of r-metHu granulocyte colony-stimulating factor (G-CSF) on the proportion of patients with metastatic poor-prognosis malignant germ cell tumors who receive full dose-intensity combination chemotherapy.
In a phase III study patients received six cycles of BEP/EP (etoposide, and cisplatin, plus or minus bleomycin) or six cycles of BOP/VIP-B (bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, bleomycin). A subset were secondarily randomized to receive or not receive filgrastim. Filgrastim 5 microg/kg/day was administered subcutaneously on days 3 through 9 after each BOP and on days 6 through 19 after each VIP, BEP, or EP cycle.
Eighty-five percent of 120 eligible patients randomized to filgrastim received at least six chemotherapy cycles compared with 70% of 130 patients randomized to not receive filgrastim (VCP = .003). Patients in the filgrastim-arm achieved significantly higher dose-intensities. Neutropenic fever occurred in 25 of 128 filgrastim-patients and in 38 of 129 non-filgrastim-patients (P = .052). Twelve and three toxic deaths occurred in the non-filgrastim- and filgrastim-arms, respectively. Nine of the 12 toxic deaths and all of the three toxic deaths were associated with febrile grade 4 neutropenia. Failure-free and overall survival were similar in both arms.
During combination chemotherapy in patients with malignant germ cell tumors, the routine use of filgrastim significantly improved the delivery of the planned treatment schedule without effect on failure-free or overall survival. The use of filgrastim was associated with a clinically important reduction in the number of toxic deaths, confined to the experimental intensified-chemotherapy schedule. This study does not support the routine use of filgrastim during standard chemotherapy with BEP.
确定重组人粒细胞集落刺激因子（G-CSF）对接受全剂量强度联合化疗的转移性预后不良恶性生殖细胞肿瘤患者比例的影响。
在一项III期研究中，患者接受六个周期的BEP/EP（依托泊苷和顺铂，加或不加博来霉素）或六个周期的BOP/VIP-B（博来霉素、长春新碱、顺铂/依托泊苷、异环磷酰胺、顺铂、博来霉素）。一组患者被二次随机分组，分别接受或不接受非格司亭。在每次BOP治疗后的第3至9天以及每次VIP、BEP或EP周期后的第6至19天，皮下注射非格司亭，剂量为5μg/kg/天。
随机分配至非格司亭组的120例符合条件的患者中，85%接受了至少六个化疗周期，而随机分配至未接受非格司亭组的130例患者中这一比例为70%（P = 0.003）。非格司亭组患者实现了显著更高的剂量强度。128例接受非格司亭治疗的患者中有25例发生中性粒细胞减少性发热，129例未接受非格司亭治疗的患者中有38例发生（P = 0.052）。未接受非格司亭组和接受非格司亭组分别有12例和3例因毒性反应死亡。12例毒性反应死亡中有9例以及3例毒性反应死亡全部与4级发热性中性粒细胞减少有关。两组的无失败生存期和总生存期相似。
在恶性生殖细胞肿瘤患者的联合化疗期间，常规使用非格司亭显著改善了计划治疗方案的实施，且对无失败生存期或总生存期无影响。非格司亭的使用与毒性反应死亡数量的临床显著减少相关，这仅限于实验性强化化疗方案。本研究不支持在BEP标准化疗期间常规使用非格司亭。
