Anticancer Section / Original Paper

Khatib A.W. · Selub S.M. · Uryvaev A. · Baranseh J. · Shai A.

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Article / Publication Details Abstract

Introduction: Fluorouracil (5-FU) pharmacokinetics are variable, leading to risk of toxicity in some patients and under-dosing in others. Therapeutic drug monitoring (TDM) 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 hours for whom 5-FU blood level was collected at least once. Response, date of progression and death were collected for patients with colon and pancreatic cancer. Results: In multivariate analysis, 5-FU blood levels 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. 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. 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.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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