Graziano S L, Valone F H, Herndon J E, Crawford J, Richards F, Rege V B, Clamon G, Green M R
Department of Medicine, SUNY-Health Science Center, Syracuse, USA.
Lung Cancer. 1996 Jun;14(2-3):315-29. doi: 10.1016/0169-5002(96)00556-9.
This Phase II study was designed to determine the efficacy of two chemotherapy regimens with G-CSF support for patients with advanced non-small cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m2 days 1-3, mesna 400 mg/m2 at 0, 4, 6 h days 1-3, cisplatin 33 mg/m2 days 1-3 or etoposide 200 mg/m2 days 1-3, cisplatin 35 mg/m2 days 1-3. Both groups received G-CSF 5 micrograms/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 47 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median survival 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or worse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For course 1, the median absolute neutrophil count nadir was 1.3, platelet nadir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligible patients receiving etoposide/cisplatin, the response rate was 21% (95% confidence interval: 11-35%) and median survival 5.8 months (95% confidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%, thrombocytopenia 58%, infection 29%. There were three treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2, platelet nadir 80 000 and incidence of febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and etoposide/cisplatin, median duration of Grade IV neutropenia was short (< or = 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full doses of drugs to be delivered on schedule, both ifosfamide/mesna/cisplatin and etoposide/cisplatin produced response rates and survival similar to other cisplatin-based regimens. In view of the significant cost of G-CSF and no obvious improvement in response rate, survival or toxicity profile, G-CSF cannot be recommended with these chemotherapy regimens for patients with advanced NSCLC.
这项II期研究旨在确定两种化疗方案联合粒细胞集落刺激因子（G-CSF）对晚期非小细胞肺癌（NSCLC）患者的疗效。101例III B期或IV期NSCLC且体能状态为0 - 1的患者被随机分组，分别接受异环磷酰胺2.0 g/m²，第1 - 3天；美司钠400 mg/m²，第1 - 3天的0、4、6小时；顺铂33 mg/m²，第1 - 3天，或依托泊苷200 mg/m²，第1 - 3天；顺铂35 mg/m²，第1 - 3天。两组均在第4天开始皮下注射G-CSF 5微克/千克，直至第11天后绝对中性粒细胞计数>10000。对于47例符合条件接受异环磷酰胺/美司钠/顺铂治疗的患者，缓解率为26%（95%置信区间：14 - 40%），中位生存期为7.5个月（95%置信区间：5.8 - 11.0个月）。3级或更严重的毒性反应为：中性粒细胞减少75%，血小板减少70%，感染21%。有2例因感染导致的治疗相关死亡。对于第1疗程，中性粒细胞计数绝对值最低点的中位数为1.3，血小板最低点为96000，发热性中性粒细胞减少的发生率为16%。对于48例符合条件接受依托泊苷/顺铂治疗的患者，缓解率为21%（95%置信区间：11 - 35%），中位生存期为5.8个月（95%置信区间：4.5 - 9.7个月）。3级或更严重的毒性反应为：中性粒细胞减少90%，血小板减少58%，感染29%。有3例因感染导致的治疗相关死亡。对于第1疗程，中性粒细胞计数绝对值最低点的中位数为0.2，血小板最低点为80000，发热性中性粒细胞减少的发生率为33%。对于异环磷酰胺/美司钠/顺铂和依托泊苷/顺铂，IV级中性粒细胞减少的中位持续时间较短（≤4天），至后续疗程的时间为21天，给药剂量>计划剂量的95%。虽然G-CSF使药物能够按时足量给药，但异环磷酰胺/美司钠/顺铂和依托泊苷/顺铂的缓解率和生存期与其他基于顺铂的方案相似。鉴于G-CSF成本高昂，且在缓解率、生存期或毒性方面无明显改善，不建议将G-CSF与这些化疗方案联合用于晚期NSCLC患者。
