1 Centre Eugène Marquis, Rennes, France.
2 Centre Paul Strauss, Strasbourg, France.
J Clin Oncol. 2019 Mar 10;37(8):658-667. doi: 10.1200/JCO.18.00050. Epub 2019 Feb 1.
No 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.
We 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 on day 1 and oxaliplatin 85 mg/m 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.
Between 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).
There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.
在接受手术切除后的局部胆道癌（BTC）中，目前尚无标准的辅助治疗方法。我们旨在评估吉西他滨和奥沙利铂化疗（GEMOX）是否会增加无复发生存期（RFS），同时保持接受手术切除的患者的健康相关生活质量（HRQOL）。
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。在 R0 或 R1 局部 BTC 切除后 3 个月内，患者被随机分配（1:1）接受吉西他滨 1000mg/m2 于第 1 天（GEMOX）和奥沙利铂 85mg/m2 于第 2 天（每 2 周周期）进行 12 个周期（实验组 A）或监测（标准组 B）。主要终点是 RFS 和 HRQOL。
2009 年 7 月至 2014 年 2 月，共纳入 196 例患者。两组的基线特征平衡。中位随访 46.5 个月（95%CI，42.6 至 49.3 个月）后，记录了 126 例 RFS 事件和 82 例死亡。两组 RFS 无显著差异（中位，实验组 A 为 30.4 个月，实验组 B 为 18.5 个月；风险比 [HR]，0.88；95%CI，0.62 至 1.25；P =.48）。全球 HRQOL 明确恶化的时间也无差异（中位，实验组 A 为 31.8 个月，实验组 B 为 32.1 个月；HR，1.28；95%CI，0.73 至 2.26；对数秩检验 P =.39）。总生存期也无差异（中位，实验组 A 为 75.8 个月，实验组 B 为 50.8 个月；HR，1.08；95%CI，0.70 至 1.66；对数秩检验 P =.74）。最严重的不良反应发生率为 3 级（实验组 A 为 62%，实验组 B 为 18%）和 4 级（实验组 A 为 11%，实验组 B 为 3%）（ P <.001）。
尽管 GEMOX 方案的耐受性和实施情况良好，但在接受手术切除的 BTC 患者中，辅助 GEMOX 并不能带来获益。
