背景:5-氟尿嘧啶(5-FU)是胃肠道癌症治疗的主要成分。在FOLFOX等多种药物治疗方案中,FOLFIRI,跟随FIRINOX,5-FU通常作为丸剂施用,随后输注。然而,在这些方案中加入5-FU丸剂的药理学原理尚不清楚,对于胃肠道癌症,还有其他有效的治疗方案,不包括推注。这项研究的目的是确定5-FU推注的遗漏是否与存活率和毒性的差异有关。
方法:从FlatironHealth的真实数据库中查询了晚期结直肠患者,胃食管,和接受一线FOLFOX的胰腺癌,FOLFIRI,并遵循FIRINOX方案。进行Cox比例风险和Kaplan-Meier分析以比较接受5-FU推注的患者和未接受5-FU推注的患者之间的生存结果。进行治疗加权逆概率(IPTW)分析以调整治疗选择偏倚。
结果:这项研究包括11,765例晚期结直肠患者(n=8,670),胃食管(n=1,481),和胰腺癌(n=1,614)。在所有一线5-FU多药方案中,10,148例(86.3%)患者接受了5-FU推注,1,617例(13.7%)没有。IPTW分析后,我们发现省略推注与总生存率的降低无关(风险比,0.99;95%CI,0.91-1.07;P=.74)。然而,省略推注与中性粒细胞减少减少相关(10.7%vs22.7%;P<0.01),血小板减少症(11.2%vs16.1%;P<0.01),治疗后使用粒细胞集落刺激因子(19.6%vs29.1%;P<0.01)。
结论:调整基线临床因素后,我们发现FOLFOX遗漏了5-FU丸,FOLFIRI,FOLFIRINOX方案与降低生存率无关,但导致毒性降低和可能的医疗保健节省。
BACKGROUND: 5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and
FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus. The purpose of this study was to determine whether omission of the 5-FU bolus was associated with a difference in survival and toxicity.
METHODS: A real-world database from Flatiron Health was queried for patients with advanced colorectal, gastroesophageal, and pancreatic cancers who received first-line FOLFOX, FOLFIRI, and
FOLFIRINOX regimens. Cox proportional hazards and Kaplan-Meier analyses were performed to compare survival outcomes between patients who received the 5-FU bolus and those who did not. Inverse probability of treatment weighted (IPTW) analysis was performed to adjust for treatment selection bias.
RESULTS: This study included 11,765 patients with advanced colorectal (n=8,670), gastroesophageal (n=1,481), and pancreatic (n=1,614) cancers. Among all first-line 5-FU multidrug regimens, 10,148 (86.3%) patients received a 5-FU bolus and 1,617 (13.7%) did not. After IPTW analysis, we found that omitting the bolus was not associated with a decrease in overall survival (hazard ratio, 0.99; 95% CI, 0.91-1.07; P=.74). However, omitting the bolus was associated with reductions in neutropenia (10.7% vs 22.7%; P<.01), thrombocytopenia (11.2% vs 16.1%; P<.01), and use of granulocyte colony-stimulating factors after treatment (19.6% vs 29.1%; P<.01).
CONCLUSIONS: After adjusting for baseline clinical factors, we found that omission of the 5-FU bolus from FOLFOX, FOLFIRI, and
FOLFIRINOX regimens was not associated with decreased survival, but resulted in decreased toxicity and possible health care savings.