Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan

Emma C Hulshof; Maarten J Deenen; Marga Nijenhuis; Bianca Soree; Nienke J de Boer-Veger; Anne-Marie Buunk; Elisa J F Houwink; Arne Risselada; Gerard A P J M Rongen; Ron H N van Schaik; Daan J Touw; Jan van der Weide; Roos van Westrhenen; Vera H M Deneer; Henk-Jan Guchelaar; Jesse J Swen

doi:10.1038/s41431-022-01243-2

Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan

Emma C Hulshof, Maarten J Deenen, Marga Nijenhuis^*, Bianca Soree, Nienke J de Boer-Veger, Anne-Marie Buunk, Elisa J F Houwink, Arne Risselada, Gerard A P J M Rongen, Ron H N van Schaik, Daan J Touw, Jan van der Weide, Roos van Westrhenen, Vera H M Deneer, Henk-Jan Guchelaar, Jesse J Swen

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

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 the anti-cancer drug irinotecan to decrease the risk of severe toxicity, such as (febrile) neutropenia or diarrhoea. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1 encoded by the UGT1A1 gene) enzyme deficiency increases risk of irinotecan-induced toxicity. Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual's starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered "essential", indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.

Original language	English
Pages (from-to)	982-987
Number of pages	6
Journal	European Journal of Human Genetics
Volume	31
Issue number	9
Early online date	28 Nov 2022
DOIs	https://doi.org/10.1038/s41431-022-01243-2
Publication status	Published - Sept 2023

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10.1038/s41431-022-01243-2

1 Erratum / corrigendum / retractions

Correction: Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between UGT1A1 and irinotecan: (European Journal of Human Genetics, (2022), 10.1038/s41431-022-01243-2)
Hulshof, E. C., Deenen, M. J., Nijenhuis, M., Soree, B., de Boer-Veger, N. J., Buunk, A. M., Houwink, E. J. F., Risselada, A., Rongen, G. A. P. J. M., van Schaik, R. H. N., Touw, D. J., van der Weide, J., van Westrhenen, R., Deneer, V. H. M., Guchelaar, H. J. & Swen, J. J., Sept 2023, In: European Journal of Human Genetics. 31, 9, p. 1088-1089 2 p.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

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Hulshof, E. C., Deenen, M. J., Nijenhuis, M., Soree, B., de Boer-Veger, N. J., Buunk, A.-M., Houwink, E. J. F., Risselada, A., Rongen, G. A. P. J. M., van Schaik, R. H. N., Touw, D. J., van der Weide, J., van Westrhenen, R., Deneer, V. H. M., Guchelaar, H.-J., & Swen, J. J. (2023). Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan. European Journal of Human Genetics, 31(9), 982-987. https://doi.org/10.1038/s41431-022-01243-2

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title = "Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan",

abstract = "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 the anti-cancer drug irinotecan to decrease the risk of severe toxicity, such as (febrile) neutropenia or diarrhoea. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1 encoded by the UGT1A1 gene) enzyme deficiency increases risk of irinotecan-induced toxicity. Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual's starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered {"}essential{"}, indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.",

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year = "2023",

month = sep,

doi = "10.1038/s41431-022-01243-2",

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Hulshof, EC, Deenen, MJ, Nijenhuis, M, Soree, B, de Boer-Veger, NJ, Buunk, A-M, Houwink, EJF, Risselada, A, Rongen, GAPJM, van Schaik, RHN, Touw, DJ, van der Weide, J, van Westrhenen, R, Deneer, VHM, Guchelaar, H-J & Swen, JJ 2023, 'Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan', European Journal of Human Genetics, vol. 31, no. 9, pp. 982-987. https://doi.org/10.1038/s41431-022-01243-2

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AU - Hulshof, Emma C

AU - Deenen, Maarten J

AU - Nijenhuis, Marga

AU - Soree, Bianca

AU - de Boer-Veger, Nienke J

AU - Buunk, Anne-Marie

AU - Houwink, Elisa J F

AU - Risselada, Arne

AU - Rongen, Gerard A P J M

AU - van Schaik, Ron H N

AU - Touw, Daan J

AU - van der Weide, Jan

AU - van Westrhenen, Roos

AU - Deneer, Vera H M

AU - Guchelaar, Henk-Jan

AU - Swen, Jesse J

PY - 2023/9

Y1 - 2023/9

N2 - 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 the anti-cancer drug irinotecan to decrease the risk of severe toxicity, such as (febrile) neutropenia or diarrhoea. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1 encoded by the UGT1A1 gene) enzyme deficiency increases risk of irinotecan-induced toxicity. Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual's starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered "essential", indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.

AB - 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 the anti-cancer drug irinotecan to decrease the risk of severe toxicity, such as (febrile) neutropenia or diarrhoea. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1 encoded by the UGT1A1 gene) enzyme deficiency increases risk of irinotecan-induced toxicity. Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual's starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered "essential", indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.

U2 - 10.1038/s41431-022-01243-2

DO - 10.1038/s41431-022-01243-2

M3 - (Systematic) Review article

C2 - 36443464

SN - 1018-4813

VL - 31

SP - 982

EP - 987

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 9

ER -

Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan

Abstract

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Research output

Correction: Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between UGT1A1 and irinotecan: (European Journal of Human Genetics, (2022), 10.1038/s41431-022-01243-2)

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