Initiating Treatment with Low Fluorouracil Dose and Titrating According to Blood Levels in Patients Treated with a 46-Hour Continuous Infusion

Ahmad Waleed Khatib, Samuel Maxwell Selub, Anton Uryvaey, Jalal Baranseh, Ayelet Shai

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Fluorouracil (5-FU) pharmacokinetics are variable, leading to a risk of toxicity in some patients and underdosing in others. Therapeutic drug monitoring of 5-FU was shown to reduce toxicity and increase efficacy. This study assessed the clinical utility of starting treatment with 70-80% of BSA calculated dose and titrating according to 5-FU blood levels and toxicity. Methods: A retrospective analysis of a prospectively collected database of 126 patients treated with regimens containing 5-FU bolus and continuous infusion for 46 h for whom the 5-FU blood level was collected at least once. Response,and date of progression, and death were collected for patients with colon and pancreatic cancer. Results: In multivariate analysis, 5-FU blood levels were correlated with 5-FU dose and with age, albeit a small effect size (coefficient = 0.007). Of patients with colon cancer treated with an initial lower 5-FU dose, 18% had a therapeutic 5-FU blood level. The median survival was similar in patients with metastatic colon cancer treated with lower doses and those treated with a full dose. Of patients with pancreatic cancer treated with lower doses, 40% had therapeutic blood levels. The median survival was 13 months in patients with metastatic pancreatic cancer treated with lower 5-FU doses. Conclusion: Starting treatment with low 5-FU dose was associated with patient survival comparable to other published data, and a sizeable percentage of patients had therapeutic blood levels. This approach can be considered, especially in elderly and frail patients.

Original languageEnglish
Pages (from-to)95-101
Number of pages7
JournalChemotherapy
Volume68
Issue number2
DOIs
StatePublished - 1 Jun 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 S. Karger AG. All rights reserved.

Keywords

  • 5-Fluorouracil
  • Adherence
  • Adverse events
  • Dihydropyrimidine dehydrogenase
  • Elderly
  • Frail
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

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