Investigators have found that administering fluorouracil (5-FU) through continuous infusion and omitting the bolus component in patients undergoing commonly used treatment regimens targeting metastatic gastrointestinal cancers may improve tolerability without reducing treatment efficacy or negatively affecting patient outcomes, according to a study published by Peng et al in JNCCN–Journal of the National Comprehensive Cancer Network.
Background
“For decades, the most effective treatment for gastrointestinal cancers was a combination of two forms of 5-FU: the 5-FU bolus injection followed by the 5-FU continuous infusion,” explained senior study author Shun Yu, MD, MS, of New York University Langone Health. “However, in the early 2000s, the standard of care evolved into multidrug regimens after it was discovered that adding to the two-component 5-FU backbone significantly improved patient outcomes. While the value of the 5-FU bolus was well established in the older single-drug regimens, its role in these newer multidrug combinations was never thoroughly tested and was largely just assumed,” he stressed.
Study Methods and Results
In the large, retrospective cohort study, the investigators analyzed the outcomes of 11,765 patients diagnosed with advanced colorectal, gastroesophageal, and pancreatic cancers across 280 cancer clinics between January 2011 and May 2022. They then determined the safety and survival rates of the patients following multiagent 5-FU–based chemotherapy with and without administration of the 5-FU bolus component. They adjusted for clinical factors such as age and comorbidities.
The investigators revealed that there was no decrease in overall survival among the 13.7% of patients who did not receive a 5-FU bolus component as part of their treatment regimen. However, these patients did experience a notable reduction in cytopenias, including neutropenia or thrombocytopenia.
Further, many practicing oncologists—particularly those who have been in practice longer or who specialize in gastrointestinal cancers—have already begun to omit the bolus. Recent shortages of 5-FU have also demonstrated the potential for reducing this bolus portion.
Conclusions
“The true value of our findings lies in the empirical evidence they provide, which supports what many of us have long suspected. The most significant benefit of this adjustment is that it makes the treatment more tolerable, potentially easing the chemotherapy experience for patients,” Dr. Yu highlighted.
“This study offers solid evidence for not using a 5-FU bolus with FOLFOX/FOLFIRI/FOLFIRINOX regimens in advanced [gastrointestinal] cancers. [Although] 5-FU is a core component of treatment regimens for many gastrointestinal cancers and has traditionally been included as a bolus in addition to a 46-hour infusion in many multiagent chemotherapy regimens, there has been no clear evidence showing that bolus 5-FU confers additional efficacy when retained with 5-FU infusion in multiagent regimens,” underscored Elena Gabriela Chiorean, MD, of Fred Hutch Cancer Center, who was not involved in the study. “This large study shows that omitting the bolus 5-FU has no detrimental effect on survival but reduces side effects and health-care costs,” she concluded.
Disclosure: The research in this study was supported in part by Merck, Genentech, Rafael Pharmaceuticals, Arcus Biosciences, Novartis, Zai Lab, Amal Therapeutics, 23andMe, AbbVie, Astellas Pharma, Atreca, Bayer, Bristol Myers Squibb/Celgene, Day One Biopharmaceuticals, Dragonfly Therapeutics, EMD Serono, HiberCell, I-MAB, Incendia Therapeutics, Incyte, Eli Lilly, Riboscience LLC, Sumitomo Dainippon Pharma, Totus Medicines, and Tyra Biosciences. For full disclosures of the study authors, visit jnccn.org.
