Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study
Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study
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DOI：
10.1200/jco.18.00050
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发表时间：
2019-03-10
影响因子：
45.3
通讯作者：
Phelip, Jean-Marc
中科院分区：
文献类型：
--
作者：
Edeline, Julien;Benabdelghani, Meher;Phelip, Jean-Marc
目的：局限性胆道癌（BTC）手术切除后，目前没有推荐标准的辅助治疗。我们的目的是评估吉西他滨和奥沙利铂化疗（GEMOX）是否会增加切除患者的无复发生存期（RFS），同时维持与健康相关的生活质量（HRQOL）。患者和方法我们在33个中心进行了一项多中心、开放标签、随机III期试验。患者在R0或R1切除局部BTC后3个月内随机分配（1:1）接受GEMOX(吉西他滨1,000 mg/m（2)在第1天，奥沙利铂85 mg/m(2)在2周周期的第2天输注）12个周期（实验组a）或监测（标准组B）。主要终点为RFS和HRQOL。结果2009年7月至2014年2月共纳入196例患者。基线特征在两组之间平衡。中位随访46.5个月（95% CI, 42.6 - 49.3个月）后，记录了126例RFS事件和82例死亡。两组患者的RFS无显著差异（A组中位数为30.4个月，B组中位数为18.5个月；风险比[HR]为0.88；95% CI为0.62 ~ 1.25;P = 0.48）。总体HRQOL最终恶化的时间没有差异（A组中位为31.8个月，B组中位为32.1个月；HR为1.28；95% CI为0.73至2.26;log-rank P = 0.39）。总生存期无差异（A组中位为75.8个月，B组中位为50.8个月；HR为1.08；95% CI为0.70 ~ 1.66;log-rank P = 0.74）。最大不良事件为3级，分别为62% （A组）和18% （B组），4级分别为11%和3% （P < 0.001）。结论尽管有足够的耐受性和递送方案，但佐剂GEMOX对切除的BTC没有益处。
PURPOSENo standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection.PATIENTS AND METHODSWe performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m(2) on day 1 and oxaliplatin 85 mg/m(2) infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL.RESULTSBetween July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio [HR], 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% (P < .001).CONCLUSIONThere was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.