背景:转移性胰腺腺癌(PAC)的预后仍然令人沮丧,吉西他滨单药治疗已成为过去十年的标准治疗方法。目前,在这种情况下使用两种一线方案:FOLFIRINOX和nab-紫杉醇+吉西他滨.关于确定吉西他滨功效的hENT1的预测值的翻译数据的增加表明,由于PAC对这种细胞毒性药物的高抗性,非吉西他滨为基础的方案在约60%的PAC患者中是有利的。这项研究旨在评估每周nab-紫杉醇联合吉西他滨或简化的LV5FU2方案在先前未经治疗的转移性PAC患者中的疗效。
方法:AFUGEM是一个两阶段,开放标签,随机化,多中心,第二阶段试验。符合纳入标准并提供书面知情同意书的PAC患者将以1:2的比例随机分配给nab-紫杉醇(125mg/m(2))加吉西他滨(1000mg/m(2))在第1天,8天和15天每28天或nab-紫杉醇(125mg/m(2))加sLV5FU2(亚叶酸400mg/m(2))每2天,总共114名患者将被随机分配到一个治疗组。主要终点是4个月时的无进展生存期。次要结果是反应率和持续时间,疾病控制,总生存率,安全,和生活质量。将评估吉西他滨(hENT1,dCK)和5-氟尿嘧啶(TS)功效的潜在生物标志物。
结论:AFUGEM试验旨在提供有关nab-紫杉醇联合吉西他滨和nab-紫杉醇联合sLV5FU2方案的疗效和耐受性的有价值信息。吉西他滨和5-氟尿嘧啶的潜在预测性生物标志物的鉴定可能驱动转移性PAC患者的治疗决策。
背景:AFUGEM在Clinicaltrials.gov:NCT01964534注册,2013年10月15日。
BACKGROUND: Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This
study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC.
METHODS: AFUGEM is a two-stage, open-label, randomized, multicenter, phase II
trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed.
CONCLUSIONS: The AFUGEM
trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC.
BACKGROUND: AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.