’Reassuring’ findings show eliminating 5-FU bolus in GI cancer does not affect survival
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Key takeaways:
- Administration of 5-FU bolus did not affect survival for patients with metastatic gastrointestinal cancer.
- Individuals who did not receive bolus experienced less toxicity.
Patients with metastatic gastrointestinal cancer may not need a 5-FU bolus as part of their treatment, according to retrospective study results.
Individuals who received standard first-line regimens without the bolus achieved similar OS as those who did while also experiencing less toxicity.
“The results were not too surprising,” Shun Yu, MD, oncologist at NYU Langone Health’s Perlmutter Cancer Center, told Healio. “Many gastrointestinal oncologists were already routinely omitting the 5-FU bolus, as its pharmacological justification had been questioned for some time. There was a prevailing suspicion that the bolus component might not be as essential as the other components in regimens like FOLFOX and FOLFIRI. It was, however, reassuring to see a large retrospective dataset confirming what we had long suspected.”
Background and methods
GI cancers are associated with substantial mortality risk. Colorectal, pancreatic and gastroesophageal malignancies accounted for 27.1% of worldwide cancer-related deaths in 2020, according to study background.
Several first-line, multidrug treatment regimens use 5-FU as a key component. It is administered both as a bolus and a continuous infusion that lasts between 46 and 48 hours.
“Pharmacokinetically, the rationale for using a bolus dose is to minimize the time required to reach a steady-state therapeutic drug concentration,” Yu and colleagues wrote. “However, 5-FU has a half-life of 8 to 20 minutes and, therefore, therapeutic levels occur quickly with infusional dosing.”
Survey results showed up to 40% of oncologists have stopped using the 5-FU bolus.
“If the omission of the bolus did not compromise treatment outcomes but did reduce side effects, it would have presented a significant chance to enhance the patient experience while also contributing to health care cost savings,” Yu told Healio.
Yu and colleagues used the nationwide Flatiron Health database to identify 11,765 patients (median age, 63 years; range, 18-85; 59.6% men; 64.2% white) diagnosed with colorectal (73.7%), pancreatic (13.7%) or gastroesophageal (12.6%) cancers between January 2011 and May 2022.
All patients received FOLFOX (68.1%), FOLFIRI (18.2%) or FOLFIRINOX (13.7%) regimens, which can include the 5-FU bolus and infusion. Most patients received the bolus (86.3%).
OS served as the primary outcome measure. Researchers also assessed toxicity.
Results and next steps
Results showed similar OS between patients who received the bolus infusion and those who did not (HR = 0.99; 95% CI, 0.91-1.07).
OS did not differ based on age, sex, ECOG performance status, cancer type, regimen, practice setting, year of treatment or dose level.
Individuals who received the bolus had an increased likelihood of developing neutropenia (22.7% vs. 10.7%; P < .01) or thrombocytopenia (16.1% vs. 11.2%; P < .01) in the 14 days after treatment.
A hjgher percentage of patients who received the bolus needed granulocyte colony-stimulating factor within 30 days of treatment (29.1% vs. 19.6%; P < .01).
Rates of anemia did not differ between the two cohorts.
Omitting the bolus “could meaningfully improve treatment tolerability for many patients,” Yu said.
Researchers acknowledged study limitations, including its retrospective nature, evaluation of 5-FU solely in an advanced setting and lack of data about specific cancer sites.
“We need a large randomized trial to confirm these findings with greater certainty,” Yu said.
For more information:
Shun Yu, MD, can be reached at shun.yu@nyulangone.org.
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