5-Fluoro uracil (5FU) (and capecitabine; a 5FU prodrug) is a uracil analogue used in the treatment of a variety of tumour types. Inside a cell, incorporation of 5FU into nascent mRNA and DNA is toxic to normal cellular metabolism. While primarily toxic to rapidly dividing tumour cells, 5FU is also toxic to normal cells. As such, 5FU dosing must be carefully considered, weighing its general toxicity against its therapeutic benefit.
DPYD encodes the enzyme dihydropyrimidine dehydrogenase (DPD). DPD catalyzes the rate limiting step in the catabolism (degradation) of uracil and thymidine (pyrimidine constituents of RNA and DNA respectively). Relevant to oncology, mutations in DPYD reduce the rate of pyrimidine (and 5FU) catabolism. In patients who are carriers of a DPYD mutation, 5FU is not cleared in a timely manner resulting in 5FU toxicity. Depending on a patient’s carrier status, initial dosing of 5FU might need to be adjusted (downward) in order to avoid/mitigate 5FU toxicity. In some cases, 5FU may be avoided altogether.
INDICATION & REFERRAL
This test is indicated for:
- Prospective testing: any patient PRIOR to receiving treatment with 5-fluoro uracil (5FU) or capecitabine.
- Retrospective testing: any patient who has had an adverse reaction to 5FU or capecitabine (known or suspected).
- Completed CGL DPYD Testing requisition form [link]
- 6mL Peripheral Blood in EDTA tube (purple top)
There are three important elements reported back to the referring physician.
1. The actual variants (if any) detected and the functional consequence the individual variant.
2. An interpretation outlining the clinical significance of the results obtained. As this is a germline test, a comment is also provided highlighting the likelihood that family members may be carriers of the variant identified in this patient (if any).
3. The predicted DPD activity score, metabolizer phenotype, and a link-out to provincial level dosing guidance.
CGL’s DPYD genotyping assay is a DNA based QPCR test able to detect and determine zygosity of six DPYD variants as noted below.
Identification of a DPYD null or reduced function allele(s) allows the treating physician to adjust the initial 5FU/capecitabine dosing (downward) according to established guidelines. For BC Cancer guidelines on Capecitabine dosing based on DPYD genotype, click here.
TURN AROUND TIME
Results are reported within ten working days from receipt of specimen and completed requisition form.
Innocenti F, et al, All you need to know about DPYD genetic testing for patients treated with flurouracil and capecitabine: a practitioner-friendly guide. JCO Oncol Pract (2020) 16:793-798 (PMID:3319722)
CPIC Guideline for fluoropyrimidines and DPYD (2020) (link)