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

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.