5-FU Bolus Omission Reduces Toxicity in Advanced GI Cancer Chemotherapy
核心洞察
A recent study involving over 11,000 patients suggests that omitting the 5-FU bolus in multidrug chemotherapy regimens for advanced gastrointestinal cancers can reduce side effects.
The omission of the 5-FU bolus did not compromise overall survival in patients with colorectal, pancreatic, or gastroesophageal malignancies.
Patients receiving the 5-FU bolus experienced significantly higher rates of neutropenia and thrombocytopenia compared to those who received continuous infusion only.
A large multicenter study indicates that modifying multi-drug chemotherapy treatments for metastatic or advanced gastrointestinal cancers by omitting the bolus component of 5-fluorouracil (5-FU) can reduce side effects without affecting survival rates. The findings, published in the Journal of the National Comprehensive Cancer Network, suggest a potential shift in how these cancers are treated, focusing on improved patient tolerability without sacrificing efficacy.
Impact of 5-FU Bolus Omission
The study, which analyzed data from over 11,000 patients across approximately 280 cancer clinics in the U.S., revealed that patients who did not receive the short, intravenous bolus injection of 5-FU as part of their FOLFOX (搜索), FOLFIRI (搜索), or FOLFIRINOX regimens experienced fewer instances of cytopenia. Cytopenia, including neutropenia and thrombocytopenia, indicates a compromised immune system and bleeding issues, respectively. According to lead researcher Shun Yu, MD, from NYU Langone Health, this adjustment could make the treatment more tolerable, easing the chemotherapy experience for patients.
Historical Context and Rationale
For decades, a standard approach in treating gastrointestinal cancers involved a 5-FU bolus injection followed by continuous infusion. However, with the advent of multi-drug regimens in the early 2000s, the role of the 5-FU bolus in these combinations was not thoroughly re-evaluated. The rationale behind the bolus dose was to rapidly achieve a steady-state therapeutic drug concentration. Given 5-FU's short half-life of 8 to 20 minutes, therapeutic levels are quickly reached through infusion alone.
Study Details and Patient Population
The study included patients aged 18 years and older diagnosed with metastatic or advanced colorectal, pancreatic, or gastroesophageal malignancy between January 2011 and May 2022. These patients received FOLFOX (搜索), FOLFIRI (搜索), or FOLFIRINOX regimens. Among the participants, 73.7% had colorectal cancer (搜索), 12.6% had gastroesophageal cancer (搜索), and 13.7% had pancreatic cancer (搜索). The majority (86.3%) received the standard-dose 5-FU bolus on the first day of treatment.
Key Findings on Toxicity and Survival
Following inverse probability treatment weighting (IPTW) analysis to reduce imbalances, patients who received the 5-FU bolus were significantly more likely to experience neutropenia (22.7% vs. 10.7%) and thrombocytopenia (16.1% vs. 11.2%). Importantly, the study found no significant difference in overall survival (OS) when the 5-FU bolus was omitted (HR, 0.99; 95% CI, 0.91–1.07; P = .74).
Expert Commentary
Chengwei Peng, MD, a medical oncologist from Northwestern Medicine, noted that the benefit of including the 5-FU bolus has not been studied as a primary endpoint in clinical trials. Peng and colleagues stated, "The phase 3 OPTIMOX1 trial in colorectal cancer (搜索) comparing FOLFOX4 (using both bolus and infusional 5-FU) vs FOLFOX7 (infusional 5-FU only) suggests that there is no additional benefit to bolus 5-FU, although this was not the primary endpoint. Retrospective studies in pancreatic cancer (搜索) comparing FOLFIRINOX vs modified FOLFIRINOX (which does not contain 5-FU bolus) have also not demonstrated survival differences. In our study, we observed no differences in survival, regardless of the specific 5-FU MDR used or the cancer subtype."
Implications for Clinical Practice
The study suggests that omitting the 5-FU bolus in first-line multidrug regimens may reduce treatment toxicity without compromising efficacy in patients with advanced gastrointestinal cancers. This approach could lead to improved tolerability and a better quality of life for patients undergoing chemotherapy.