New York University, New York, NY.
Northwestern University, Chicago, IL.
J Natl Compr Canc Netw. 2024 Sep 5;22(8):521-527. doi: 10.6004/jnccn.2024.7029.
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.
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.
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).
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.
5-氟尿嘧啶（5-FU）是胃肠道癌症治疗的主要成分。在 FOLFOX、FOLFIRI 和 FOLFIRINOX 等多药方案中，5-FU 通常作为推注给药，随后进行输注。然而，在这些方案中加入 5-FU 推注的药理学原理尚不清楚，并且还有其他针对胃肠道癌症的有效方案不包括推注。本研究的目的是确定省略 5-FU 推注是否与生存和毒性差异相关。
从 Flatiron Health 的真实世界数据库中查询接受一线 FOLFOX、FOLFIRI 和 FOLFIRINOX 方案治疗的晚期结直肠癌、胃食管和胰腺癌患者。使用 Cox 比例风险和 Kaplan-Meier 分析比较接受 5-FU 推注和未接受 5-FU 推注的患者的生存结局。进行逆概率治疗加权（IPTW）分析以调整治疗选择偏倚。
这项研究包括 11765 名患有晚期结直肠癌（n=8670）、胃食管（n=1481）和胰腺（n=1614）癌症的患者。在所有一线 5-FU 多药方案中，10148 名（86.3%）患者接受了 5-FU 推注，1617 名（13.7%）患者未接受。经过 IPTW 分析后，我们发现省略推注并不会降低总生存率（风险比，0.99；95%置信区间，0.91-1.07；P=.74）。然而，省略推注与中性粒细胞减少症（10.7%比 22.7%；P<.01）、血小板减少症（11.2%比 16.1%；P<.01）和治疗后粒细胞集落刺激因子的使用减少（19.6%比 29.1%；P<.01）相关。
在调整基线临床因素后，我们发现从 FOLFOX、FOLFIRI 和 FOLFIRINOX 方案中省略 5-FU 推注与生存率降低无关，但可降低毒性并可能节省医疗保健费用。
