ISOPP CAPhO 2025 Symposium: Using Pharmacogenetics (PGx) and Therapeutic Drug Monitoring (TDM) to Address Under- and Overdosing with 5-fluorouracil (5FU) in Patients with Cancer

5-Fluorouracil (5FU) is the backbone of anticancer treatment in many solid tumours, with approx. 2 million people are treated with 5FU each year. Studies have shown that approx. ~40-60% of patients were underdosed, and ~10-20% were overdosed, when dosed based on body surface area (BSA). 5FU has a narrow therapeutic index and marked intra-patient pharmacokinetic variability, which is partially explained by PGx. The success of implementing upfront PGx program for DPYD genotyping in clinical oncology practice to prevent serious and fatal 5FU toxicities was proven feasible. However, concerns with upfront PGx dose reductions especially for DPYD intermediate metabolisers, may compromise 5FU efficacy, leading to poorer cancer outcomes. Hence, the use of TDM should be considered to supplement PGx testing, to guide dose modifications to dose 5FU safely and effectively in cancer patients. This presentation will showcase final and interim results from prospective, multisite clinical trials (PREDICT 5FU and PRECISION) respectively, with applied PGx and TDM in clinical oncology practice.

Learning Objectives

1. Describe the evidence and challenges for integrating 5FU therapeutic drug monitoring (TDM) into routine clinical oncology practice.
2. Explain the integration of pharmacogenetics (PGx) and TDM testing (including peripheral and finger prick sampling) as part of clinical practice (results from PREDICT 5FU and PRECISION multisite clinical trials).
3. Identify the challenges with upfront dose reduction for DPYD intermediate metabolisers according to PGx testing and how TDM was utilised to dose escalate according to area under the curve (AUC) Level(s).