Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin Plus Irinotecan in Patients with Previously Untreated Advanced Gastric Cancer
Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin Plus Irinotecan in Patients with Previously Untreated Advanced Gastric Cancer
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氟尿嘧啶和甲酰四氢叶酸加伊立替康每两周一次治疗方案治疗既往未经治疗的晚期胃癌患者的 II 期试验
DOI：
10.1179/joc.2007.19.5.570
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发表时间：
2007
影响因子：
1.8
通讯作者：
L. Manzione
中科院分区：
文献类型：
--
作者：
G. Rosati;S. Cordio;G. Caputo;S. Condorelli;D. Germano;M. Mattina;P. Amadio;Giorgio Reggiardo;L. Manzione
目的探讨5-氟尿嘧啶（5-FU）、亚叶酸钙（LV）联合伊立替康（CPT-11）双周方案治疗初治晚期胃癌（AGC）的疗效和安全性。本试验共纳入50例AGC患者（男性/女性35/15;中位年龄= 65），其中无一例接受过晚期疾病化疗。15例患者（30%）为70岁或以上。在其累积时，开始细胞毒性化疗，包括治疗第1天和第2天LV 100 mg/m2（2小时静脉输注），随后5-FU 400 mg/m2（推注）和5-FU 600 mg/m2（22小时连续输注），以及第1天CPT-11 180 mg/m2（1小时输注）。每2周重复一次疗程，直至出现疾病进展、不可接受的毒性或撤回知情同意。所有患者均进行了毒性评估，50例中有48例进行了反应评估，至少完成了四个疗程的化疗。2例患者（4%，意向治疗）达到完全缓解，16例（32%）达到部分缓解（总缓解率，36%; 95%置信区间[CI]：22%-50%）。24例患者（48%）病情稳定，6例患者（16%）进展。中位至进展时间为8个月（95% CI：6-10个月），中位总生存期为14个月（95% CI：6-22个月）。在<70岁和70岁或以上的患者亚组之间，疗效无显著差异。发生1例中毒死亡。治疗耐受性一般为轻至中度，易于治疗，主要3/4级毒性为中性粒细胞减少（32%）、腹泻（16%）和贫血（8%）。3-4级中性粒细胞减少症是唯一的治疗相关严重不良事件，在年龄大于≤70岁的患者中显著更常见（分别为53.3% vs 22.8%; P = 0.03）。我们的数据表明，在未经治疗的AGC患者中，LV和5-FU加CPT-11的双周方案是有效的，并且具有可接受的安全性特征。在III期临床试验中对该方案进行进一步评价似乎是必要的。
Abstract To investigate the therapeutic value and safety of the biweekly regimen of 5-fluorouracil (5-FU) and leucovorin (LV) plus irinotecan (CPT-11) in patients with previously untreated advanced gastric cancer (AGC). A total of 50 patients (M/F 35/15; median age = 65) with AGC, none of whom had received chemotherapy for advanced disease, were accrued in this trial. Fifteen patients (30%) were 70 years old or older. At the time of their accrual, cytotoxic chemotherapy, consisting of LV 100 mg/m2 (2-hour i.v. infusion) followed by 5-FU 400 mg/m2 (bolus) and 5-FU 600 mg/m2 (22-hour continuous infusion) on therapeutic days 1 and 2 plus CPT-11 180 mg/m2 (1-hour infusion) on day 1, was initiated. Treatment courses were repeated every 2 weeks until evidence of progressive disease, unacceptable toxicity or withdrawal of consent. All patients were assessable for toxicity and 48 of 50 for response evaluation, having completed at least four courses of chemotherapy. Complete response was achieved in 2 patients (4%, intent to treat) and partial response in 16 (32%) (overall response rate, 36%; 95% confidence interval [CI]: 22%-50%). Twenty-four patients (48%) had stable disease and 6 patients (16%) progressed. The median time to progression was 8 months (95% CI: 6-10 months) and median overall survival 14 months (95% CI: 6-22 months). Between the subgroups of patients <70 years old and 70 or older, there were no significant differences in efficacy. One toxic death occurred. Treatment tolerance was generally mild to moderate and easy to treat. The main grade 3/4 toxicities were neutropenia (32%), diarrhea (16%), and anemia (8%). Grade 3-4 neutropenia was the only treatment-related serious adverse event significantly more common in patients older than those aged ≤70 (53.3% vs 22.8%, respectively; P = 0.03). Our data suggest that the biweekly regimen of LV and 5-FU plus CPT-11 in untreated patients with AGC is active and has an acceptable safety profile. Further evaluation of this regimen seems to be warranted in a phase III trial.