PHC-020 Pharmacokinetically Guided Dose Adjustment of 5-Fluorouracil (5-FU) in Gastrointestinal Cancer Patients. (12th March 2013)

• Record Type: Journal Article
• Authors: Egüés, A; Aldaz, A; Marin, M; Alzueta, N; Zufia, L; Bermejo, A
• Is Part Of: European journal of hospital pharmacy. Volume 20(2013)Supplement 1
• Page Start: A132
• Page End: A132
• Publication Date: 2013-03-12
• Subjects: Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2013-000276.365
• Languages: English
• ISSNs: 2047-9956

Abstract

Abstract : Background: Appropriate dosing of chemotherapeutic drugs is critical to reducing mortality and increasing progression-free survival. 5-fluorouracil (5-FU) is a widely used chemotherapeutic drug in gastrointestinal cancer. The standard approach to dosing 5-FU is based on body surface area (BSA). However, BSA does not account for many of the factors that are responsible for 5-FU clearance such as age, gender, genotype, disease state, drug-drug interactions, organ dysfunction and co-morbidities. Clinical evidence indicates a strong correlation between both toxicity and therapeutic efficacy and total 5-FU exposure expressed as area under the curve (AUC) concentration. This evidence make 5-FU a good candidate for pharmacokinetic (PK)-guided dosing. Purpose: To evaluate the role of therapeutic drug monitoring (TDM) of 5-FU in daily clinical oncology practise. Materials and Methods: Prospective study of adult patients diagnosed with gastrointestinal cancer treated with infusion schedule regimes based on high doses of 5-FU (2.5–3.2 g/m² in 24–46 h infusion) in a university hospital. All patients were included regardless of disease state or general clinical status. Individual pharmacokinetic parameters were calculated based on anthropometrics and history of 5-FU administration using the Bayesian software programme (USC*Pack). In the first cycle the dose was calculated using the BSA, and subsequent doses were adjusted to an optimal target AUC of 30–35 mg·h/L. Results: Fifty-four patients were included in the study. Male/female ratio was 31/23, and average age and weight were 60.9 ± 12.8 years and 72.2 ± 16.9 Kg. Mean estimated pharmacokinetic parameters for volume of distribution and 5-FU clearance were 0.49 ± 0.08 L/Kg and 203 ± 68.6 L/h, respectively. To achieve the target AUC of 30–35 mg·h/L, the dose had to be increased in 33 (86.8%) patients and adjusted downward in 5 (13%). No adjustment was needed in 16 patients (29.6%).When the estimate was based on BSA, 30 patients (55.6%) had AUC < 25 mg·h/L. Conclusions: BSA-based 5-FU dosing approaches are limited when it comes to achieving optimal plasma levels in most patients. Pharmacokinetically guided dosing represents a better strategy to improve the efficacy and safety of 5-FU. No conflict of interest.