Analysis of the impact of eliminating bolus 5-fluorouracil in metastatic colorectal cancer

Autor: Chengwei Peng, Saad Saffo, Michael Shusterman, Daniel Jacob Becker, Jordan Berlin, Paul Eliezer Oberstein, Anil Nagar, Shun Yu
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Oncology. 41:59-59
ISSN: 1527-7755
0732-183X
Popis: 59 Background: 5-Fluorouracil (5-FU) is a component of first-line treatment regimens for metastatic colorectal cancer (mCRC). Historically, 5-FU is administered as a bolus followed by an infusion. However, the bolus dose adds substantial toxicity and is often withheld in patients with limited functional status or high-risk comorbidities, but its impact on treatment outcomes remains unclear. Small studies suggest that it may be omitted. The aim of this study was to determine whether omission of the 5-FU bolus is associated with a difference in overall survival (OS). Methods: An electronic health record-derived national multicenter oncology database from Flatiron Health was queried to select patients with mCRC who received a first-line 5-FU-containing regimen. Demographics, relevant labs, treatment details, and survival outcomes were collected. Propensity score (PrS) matching and OS analysis were performed incorporating age, race, sex, ECOG score, combination drug regimen, and baseline creatinine and bilirubin. Variables with p < 0.10 in univariable Cox proportional hazards models were included in the multivariable analysis. Results: We included 9741 patients with mCRC who received 5-FU-based regimens. All individuals received a 5-FU infusion, and 7901 (81%) also received a 5-FU bolus. Among our entire cohort, 43% were female, 23% were > 70 years, 66% were white, and 89% had ECOG ≤ 1. Over a median follow-up time of 19 months, 5847 patients (60%) died. In the unmatched univariable (HR 0.94, 95% CI 0.88-1.00, p = 0.06) and multivariable (aHR 0.85, 95% CI 0.93-1.06, p = 0.85) analyses, there was no association between the use of bolus 5-FU and OS. A number of factors were associated with an increased risk of death, including older age, high ECOG scores, and elevated bilirubin or creatinine levels. Similarly, in our PrS-matched dataset (n = 6126), the use of a 5-FU bolus was not associated with OS (HR 0.98; 95% CI 0.91-1.06; p = 0.64). Conclusions: The findings of our PrS-matched multicenter cohort study indicate that, after adjusting for host and treatment factors, 5-FU bolus dosing was not associated with an overall survival benefit among patients with mCRC. These results suggest that, in mCRC, the addition of a 5-FU bolus does not appear to add efficacy to regimens utilizing infusional 5-FU. Future work is necessary to determine the role of bolus dosing in the adjuvant setting and its impact on other clinically-relevant outcomes.
Databáze: OpenAIRE
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