Page 219 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

DPYD variant
DPYD*2A (c.1905+1G>A) DPYD*13 (c.1679T>G) c.2846A>T
c.1236G>A
Initial dose reduction (%)
50 50
5025a 25
Inclusion in screening program
April 15th, 2013 October 10th, 2013 October 10th, 2013 May 28th, 2014
Patients screened
529
440
440
254
Evaluating the implementation of prospective DPYD genotyping
if the oncologist followed the dose advice. The genotyping data of the laboratory of CPT was used to determine the patients carrying a DPYD variant. Prospective execution of the genotyping could be determined by comparing the genotyping date and start date of the therapy. Regular drug regimens and notations of dose reductions in the medical records were searched to check applied dose reductions.
After completion of the study, an explorative analysis was executed in order to describe the course of toxicity in relation to the provided dose recommendations. In order to perform this analysis, toxicity information regarding the 5-FU or capecitabine therapy was retrieved from the EMR for patients with a DPYD variant. Toxicity was scored by the oncologists using the National Cancer Institute common terminology criteria for adverse events (CTC-AE), version 4.03.19
Results
The implementation of the prospective screening program for DPYD
The prospective DPYD screening program was implemented on 15 April 2013 (study start
date) at LUMC. From this date until 13 December 2014 (study end date) 540 patients
were genotyped for DPYD variants at LUMC. Initially, patients were screened only for the 8 presence of the DPYD*2A variant. Later on DPYD*13, c.2846A>T and c.1236G>A were added
to the DPYD screening. An overview is shown in Table 1. After removal of duplicate or invalid records, 529 evaluable genotyped patients remained. Of these 529 patients, 275 patients
were patients treated at the LUMC and 254 patients were treated at other hospitals, but genotyped as a service provided by the department of CPT of the LUMC. The dose reductions
that were advised for each individual DPYD variant are displayed in Table 1.
Table 1. Recommended reductions of initial 5-fluorouracil or capecitabine dose
Advice given by CPIC and DPWG guidelines at the time the variant was added to the routine screening.
a The dose reduction advice for c.2846A>T has been updated to 25% in February 2015.
A total of 2,498 records of 5-FU or capecitabine prescriptions prior to 31 December 2014 were found. After removal of duplicates, invalid records (e.g., incomplete data) or patients not meeting eligibility criteria (e.g., prescription prior to April 2013), 337 patients remained who were prescribed 5-FU (16%) or capecitabine (84%) for the first time at LUMC within the study period.
Genotyped patients were compared with patients who were prescribed 5-FU or capecitabine, resulting in 236 matching patients. Thirty-nine patients were genotyped for DPYD, but were not prescribed 5-FU or capecitabine. Also, 101 patients were prescribed
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