Tibaldi C, Ricci S, Russo F, Bernardini I, Galli L, Chioni A, Orlandini C, Grosso A M, Pegna A Lopes, Fabbri A, Innocenti F, Ferrari K, Tognarini L, Conte P F, Falcone A
Division of Medical Oncology, Department of Oncology, Livorno, Italy.
Lung Cancer. 2005 Apr;48(1):121-7. doi: 10.1016/j.lungcan.2004.10.008. Epub 2004 Dec 10.
Gemcitabine is usually administered at a planned dose-intensity (DI) from 750 to 800 mg/m2/week. Preclinical data have suggested a possible dose-response relationship of gemcitabine. A multicenter phase II study was conducted to evaluate the activity in terms of no progression rate (complete responses+partial responses+stable diseases) of gemcitabine administered at an increased DI (1000 mg/m2/week) in elderly advanced non-small-cell lung cancer (NSCLC) patients. Secondary endpoints were to evaluate tolerability, progression free survival and overall survival. Elderly (age>or=70 years) chemo-naive advanced NSCLC patients, ECOG PS 0-2, were treated with intravenous gemcitabine 1500 mg/m2 intravenous (30 min infusion) on days 1 and 8 every 21 days for four courses. One hundred and twenty-two patients with a median age of 75 years (range 70-84) entered the study. The following grade 3 (NCI-CTC) haematological toxicities were reported (percent of patients): neutropenia 2.4%, thrombocytopenia 1.6%, anaemia 2.4%. No grades 3-4 non-haematological toxicities were observed. Among 111 evaluable patients 52 (46.8%) no progressions, 17 (15.3%) partial responses (WHO criteria), 35 (31.5%) stable diseases and 59 (53.2%) progressions were observed. Median time to progression was 3.2 months and median duration of survival was 5.4 months. The overall 1-year survival rate was 27%. Although increased dose-intensity of gemcitabine in elderly NSCLC patients is feasible without severe toxicities, this does not seem to be associated with an increased activity and efficacy in comparison to standard gemcitabine regimens with lower dose-intensities.
吉西他滨通常按计划的剂量强度（DI）750至800mg/m²/周给药。临床前数据提示了吉西他滨可能存在剂量反应关系。开展了一项多中心II期研究，以评估在老年晚期非小细胞肺癌（NSCLC）患者中增加剂量强度（1000mg/m²/周）给予吉西他滨时的无进展率（完全缓解+部分缓解+疾病稳定）方面的活性。次要终点是评估耐受性、无进展生存期和总生存期。年龄≥70岁、未接受过化疗的老年晚期NSCLC患者，ECOG体能状态0-2，每21天在第1天和第8天接受静脉注射吉西他滨1500mg/m²（30分钟输注），共四个疗程。122例中位年龄75岁（范围70-84岁）的患者进入研究。报告了以下3级（NCI-CTC）血液学毒性（患者百分比）：中性粒细胞减少2.4%，血小板减少1.6%，贫血2.4%。未观察到3-4级非血液学毒性。在111例可评估患者中，观察到52例（46.8%）无进展，17例（15.3%）部分缓解（WHO标准），35例（31.5%）疾病稳定和59例（53.2%）进展。中位至进展时间为3.2个月，中位生存期为5.4个月。总体1年生存率为27%。尽管在老年NSCLC患者中增加吉西他滨的剂量强度可行且无严重毒性，但与较低剂量强度的标准吉西他滨方案相比，这似乎并未带来活性和疗效的增加。
