Skipping 5-FU Bolus Enhances Chemo Tolerance in GI Cancers

TOPLINE: 

Omitting the 5-fluorouracil (5-FU) bolus from multidrug regimens in patients with advanced gastrointestinal cancers reduces toxicities, such as cytopenia, and does not affect overall survival.

METHODOLOGY:

• The National Comprehensive Cancer Network clinical practice guidelines for gastric cancer recommend 5-FU multidrug regimens, such as FOLFOX, FOLFIRI, and FOLFIRINOX, which involve a short intravenous bolus of 5-FU followed by a prolonged infusion. However, 20%-40% of oncologists reported skipping 5-FU bolus.
• To evaluate the impact of 5-FU bolus on overall survival and toxicity, researchers assessed 11,765 patients with advanced gastrointestinal cancers who received frontline treatment with FOLFOX (n = 8014), FOLFIRI (n = 2137), or FOLFIRINOX (n = 1614) regimens.
• The median age was 63 years, 64.2% were White, and 59.6% were men; 8670 patients had colorectal, 1481 had gastroesophageal, and 1614 had pancreatic cancers.
• Of all participants, 10,148 received 5-FU bolus on the first day of treatment. The bolus was administered to 90.4% of patients who received FOLFOX, 89.2% of those who received FOLFIRI, and 61.6% of those who received FOLFIRINOX.
• Study outcomes included overall survival; rates of neutropenia, anemia, and thrombocytopenia within 14 days; and use of granulocyte colony-stimulating factor use within 30 days of treatment.

TAKEAWAY:

Initial unadjusted analyses indicated that patients receiving the 5-FU bolus had longer overall survival than those who did not (20.3 vs 14 months; hazard ratio [HR], 0.74; P P = .74).

• Patients who received the bolus experienced higher rates of neutropenia (22.7% vs 10.7%; P < .01) and thrombocytopenia (16.1% vs 11.2%; P < .01) within 14 days of treatment than those who did not receive bolus. The risks remained significant after adjustments for oxaliplatin and irinotecan doses.
• Also, a greater proportion of patients who received bolus needed granulocyte colony-stimulating factors (29.1% vs 19.6%; P < .01) within 30 days.
• Prescribing practices for 5-FU-based regimens shifted over time, with patients treated without the bolus increasing from 9% to 12% for FOLFOX, 10% to 13% for FOLFIRI, and most notably, from 9% to 61% for FOLFIRINOX between 2014 and 2021.

IN PRACTICE:

“The most significant benefit of this adjustment is that it makes the treatment more tolerable, potentially easing the chemotherapy experience for patients,” study author Shun Yu, MD, MS, said in a press release. “While the value of the 5-FU bolus was well established in the older single drug regimens, its role in these newer multi-drug combinations was never thoroughly tested and was largely just assumed.”

SOURCE:

The study was led by Chengwei Peng, MD, New York University, New York. It was published online on September 5, in the JNCCN.

LIMITATIONS:

The retrospective study design has inherent biases. The findings only measured outcomes in the metastatic/advanced setting, therefore conclusions might not be applicable in the adjuvant settings. Also, information on disease sites and oligometastatic cases was not available, which could affect outcomes.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.