Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
Summary
The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD\*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD\*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.
Timeline
- Start
- 2007-05
- Primary completion
- 2011-10
- Completion
- 2011-10
Outcome
Met primary endpoint
paper The risk of grade ≥ 3 toxicity was thereby significantly reduced from 73% (95% CI, 58% to 85%) PMID 26573078 ↗
paper to 28% (95% CI, 10% to 53%) by genotype-guided dosing (P < .001) PMID 26573078 ↗
Publications
- Knikman JE, Lopez-Yurda M, Meulendijks D, Deenen MJ, Schellens JHM, Beijnen J, Cats A, Guchelaar HJ. A Nomogram to Predict Severe Toxicity in DPYD Wild-Type Patients Treated With Capecitabine-Based Anticancer Regimens. Clin Pharmacol Ther. 2024 Feb;115(2):269-277. doi: 10.1002/cpt.3100. Epub 2023 Nov 29.
- Meulendijks D, van Hasselt JGC, Huitema ADR, van Tinteren H, Deenen MJ, Beijnen JH, Cats A, Schellens JHM. Renal function, body surface area, and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care. Eur J Cancer. 2016 Feb;54:120-130. doi: 10.1016/j.ejca.2015.10.013. Epub 2016 Jan 4.
- Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. Epub 2015 Nov 16.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Capecitabine | Small molecule | — | — |
| Subject | fluorouracil | Small molecule | — | — |