On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry
On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry
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DOI：
10.6004/jnccn.2016.0148
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发表时间：
2016-11-01
影响因子：
13.4
通讯作者：
Rivera, Fernando
中科院分区：
文献类型：
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作者：
Carmona-Bayonas, Alberto;Jimenez-Fonseca, Paula;Rivera, Fernando
背景资料：对于不适合接受曲妥珠单抗治疗的晚期胃癌（AGC）患者的一线化疗，目前尚无共识。本研究的目的是通过分析国家胃癌登记处来评估三联与三联的疗效和耐受性。患者和方法：纳入了2008年至2016年期间接受多药化疗但未联合曲妥珠单抗治疗的AGC患者。使用3种方法比较三联体与双联体的效应：考克斯比例风险回归、倾向评分匹配（PSM）和粗化精确匹配（CEM）。结果：共招募了970例患者（双胞胎：n=569;三胞胎：n=401）。在多变量考克斯模型中，使用三联体与更好的总生存期（OS）相关，风险比（HR）为0.84（95% CI，0.72-0.98; P= 0.035）。在PSM之后，样本包含340对。OS显著增加，11.14个月（95% CI，9.60-12.68）vs 9.60个月（95% CI，8.44-10.75），有利于三胎（HR，0.77; 95% CI，0.65-0.92;分层对数秩检验，P= 0.004）。基于蒽环类药物（HR，0.78; 95% CI，0.64-0.94）或基于紫杉醇的三联治疗（HR，0.78; 95% CI，0.60-1.009）的效果似乎相当。应用CEM算法后趋势相似，HR为0.78（95% CI，0.63-0.97; P= 0.03）。三联疗法是可行的，相对剂量强度超过85%，除了顺铂在DCX（多西他赛，顺铂，卡培他滨）。三胞胎总体上有更严重的毒性，尤其是血液学、肝脏和粘膜不良事件。结论：由于回顾性研究的局限性，研究了一组异质性的化疗方案，我们发现三联方案在日常实践中是可行的，并且与疗效的谨慎获益相关，但代价是毒性的中度增加。
Background: There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients and Method: Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). Results: A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72-0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60-12.68) versus 9.60 months (95% CI, 8.44-10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65-0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64-0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60-1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63-0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. Conclusions: With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity.