دورية
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction of DPYDand fluoropyrimidines
العنوان: | Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction of DPYDand fluoropyrimidines |
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المؤلفون: | Lunenburg, Carin A. T. C., van der Wouden, Cathelijne H., Nijenhuis, Marga, Crommentuijn-van Rhenen, Mandy H., de Boer-Veger, Nienke J., Buunk, Anne Marie, Houwink, Elisa J. F., Mulder, Hans, Rongen, Gerard A., van Schaik, Ron H. N., van der Weide, Jan, Wilffert, Bob, Deneer, Vera H. M., Swen, Jesse J., Guchelaar, Henk-Jan |
المصدر: | European Journal of Human Genetics: EJHG; April 2020, Vol. 28 Issue: 4 p508-517, 10p |
مستخلص: | 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 DPYDgene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYDvariants, 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 DPYDgenotype, 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, DPYDgenotyping is considered “essential”, therefore directing DPYDtesting prior to initiating fluoropyrimidines. |
قاعدة البيانات: | Supplemental Index |
تدمد: | 10184813 14765438 |
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DOI: | 10.1038/s41431-019-0540-0 |