dc.contributor.author | Lau, DK | |
dc.contributor.author | Fong, C | |
dc.contributor.author | Arouri, F | |
dc.contributor.author | Cortez, L | |
dc.contributor.author | Katifi, H | |
dc.contributor.author | Gonzalez-Exposito, R | |
dc.contributor.author | Razzaq, MB | |
dc.contributor.author | Li, S | |
dc.contributor.author | Macklin-Doherty, A | |
dc.contributor.author | Hernandez, MA | |
dc.contributor.author | Hubank, M | |
dc.contributor.author | Fribbens, C | |
dc.contributor.author | Watkins, D | |
dc.contributor.author | Rao, S | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Starling, N | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-08-04T13:25:09Z | |
dc.date.available | 2023-08-04T13:25:09Z | |
dc.date.issued | 2023-04-26 | |
dc.identifier | ARTN 380 | |
dc.identifier | 10.1186/s12885-023-10857-8 | |
dc.identifier.citation | BMC Cancer, 2023, 23 (1), pp. 380 - | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5925 | |
dc.identifier.eissn | 1471-2407 | |
dc.identifier.eissn | 1471-2407 | |
dc.identifier.doi | 10.1186/s12885-023-10857-8 | |
dc.description.abstract | BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of fluoropyrimidines. Variations in the encoding DPYD gene are associated with severe fluoropyrimidine toxicity and up-front dose reductions are recommended. We conducted a retrospective study to evaluate the impact of implementing DPYD variant testing for patients with gastrointestinal cancers in routine clinical practice in a high volume cancer centre in London, United Kingdom. METHODS: Patients receiving fluoropyrimidine chemotherapy for gastrointestinal cancer prior to, and following the implementation of DPYD testing were identified retrospectively. After November 2018, patients were tested for DPYD variants c.1905+1G>A (DPYD*2A), c.2846A>T (DPYD rs67376798), c.1679T>G (DPYD*13), c.1236G>A (DPYD rs56038477), c.1601G>A (DPYD*4) prior to commencing fluoropyrimidines alone or in combination with other cytotoxics and/or radiotherapy. Patients with a DPYD heterozygous variant received an initial dose reduction of 25-50%. Toxicity by CTCAE v4.03 criteria was compared between DPYD heterozygous variant and wild type carriers. RESULTS: Between 1st December 2018 and 31st July 2019, 370 patients who were fluoropyrimidine naïve underwent a DPYD genotyping test prior to receiving a capecitabine (n = 236, 63.8%) or 5FU (n = 134, 36.2%) containing chemotherapy regimen. 33 patients (8.8%) were heterozygous DPYD variant carriers and 337 (91.2%) were wild type. The most prevalent variants were c.1601G > A (n = 16) and c.1236G > A (n = 9). Mean relative dose intensity for the first dose was 54.2% (range 37.5-75%) for DPYD heterozygous carriers and 93.2% (42.9-100%) for DPYD wild type carriers. Overall grade 3 or worse toxicity was similar in DPYD variant carriers (4/33, 12.1%) as compared to wild-type carriers (89/337, 25.7%; P = 0.0924). CONCLUSIONS: Our study demonstrates successful routine DPYD mutation testing prior to the initiation of fluoropyrimidine chemotherapy with high uptake. In patients with DPYD heterozygous variants with pre-emptive dose reductions, high incidence of severe toxicity was not observed. Our data supports routine DPYD genotype testing prior to commencement of fluoropyrimidine chemotherapy. | |
dc.format | Electronic | |
dc.format.extent | 380 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.relation.ispartof | BMC Cancer | |
dc.rights.uri | https://creativecommons.org/publicdomain/zero/1.0/ | |
dc.subject | 5-fluorouracil | |
dc.subject | Capecitabine | |
dc.subject | DPYD | |
dc.subject | Dihydropyrimidine dehydrogenase | |
dc.subject | Pharmacogenomics | |
dc.subject | Humans | |
dc.subject | Dihydrouracil Dehydrogenase (NADP) | |
dc.subject | Retrospective Studies | |
dc.subject | Fluorouracil | |
dc.subject | Pharmacogenetics | |
dc.subject | Capecitabine | |
dc.subject | Genotype | |
dc.subject | Gastrointestinal Neoplasms | |
dc.title | Impact of pharmacogenomic DPYD variant guided dosing on toxicity in patients receiving fluoropyrimidines for gastrointestinal cancers in a high-volume tertiary centre. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-04-17 | |
dc.date.updated | 2023-08-04T13:24:31Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1186/s12885-023-10857-8 | |
rioxxterms.licenseref.startdate | 2023-04-26 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37101114 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.) | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/15/16 Starting Cohort | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Aetiological Epidemiology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1186/s12885-023-10857-8 | |
pubs.volume | 23 | |
icr.researchteam | Aetiological Epidemiology | |
icr.researchteam | Medicine (RMH) | |
dc.contributor.icrauthor | Macklin-Doherty, Aislinn | |
icr.provenance | Deposited by Mr Arek Surman on 2023-08-04. Deposit type is initial. No. of files: 1. Files: Impact of pharmacogenomic DPYD variant guided dosing on toxicity in patients receiving fluoropyrimidines for gastrointestina.pdf | |