TY - JOUR
T1 - Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction of DPYD and fluoropyrimidines
AU - Lunenburg, Carin A.T.C.
AU - van der Wouden, Cathelijne H.
AU - Nijenhuis, Marga
AU - Crommentuijn-van Rhenen, Mandy H.
AU - de Boer-Veger, Nienke J.
AU - Buunk, Anne Marie
AU - Houwink, Elisa J.F.
AU - Mulder, Hans
AU - Rongen, Gerard A.
AU - van Schaik, Ron H.N.
AU - van der Weide, Jan
AU - Wilffert, Bob
AU - Deneer, Vera H.M.
AU - Swen, Jesse J.
AU - Guchelaar, Henk Jan
N1 - Funding Information:
Funding The U-PGx consortium received funding from the European Community’s Horizon 2020 Programme under grant agreement No. 668353 (U-PGx). The DPWG received funding from the Royal Dutch Pharmacists Association. CL was previously supported by an unrestricted grant from Roche Pharmaceuticals. There was no involvement in the study design, data collection, analysis or interpretation of the data.
Publisher Copyright:
© 2019, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4
Y1 - 2020/4
N2 - Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual’s starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered “essential”, therefore directing DPYD testing prior to initiating fluoropyrimidines.
AB - Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual’s starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered “essential”, therefore directing DPYD testing prior to initiating fluoropyrimidines.
UR - http://www.scopus.com/inward/record.url?scp=85075385396&partnerID=8YFLogxK
U2 - 10.1038/s41431-019-0540-0
DO - 10.1038/s41431-019-0540-0
M3 - Article
C2 - 31745289
AN - SCOPUS:85075385396
SN - 1018-4813
VL - 28
SP - 508
EP - 517
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 4
ER -