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

Catharina Hospital
Royal Dutch Pharmacists Association (KNMP)
Pharmacy Boterdiep
Pharmacy De Katwijkse Apotheek
Institute for Risk Assessment Sciences, Utrecht University, The Netherlands; Leiden University Medical Centre, Leiden University, The Netherlands.
Canisius Wilhelmina Hospital
Radboud University Medical Center
Erasmus University Medical Center Rotterdam
University Medical Center Groningen
St. Jansdal Hospital
Department of Psychiatry
Leiden University Medical Center

Research output: Contribution to journal › 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

Bibliographical note

Funding Information:
The U-PGx consortium received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 668353. The DPWG received funding from the Royal Dutch Pharmacists Association.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to European Society of Human Genetics.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Colorectal-cancer
Efficacy
Japanese
Neutropenia
Polymorphisms
Risk
Safety
Ugt1a1-asterisk-28 genotype
Variants

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10.1038/s41431-022-01243-2

s41431-022-01243-2Final published version, 553 KBLicence: Taverne

Cite this

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

note = "Funding Information: The U-PGx consortium received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement No. 668353. The DPWG received funding from the Royal Dutch Pharmacists Association. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to European Society of Human Genetics.",

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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 - 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

N1 - Funding Information: The U-PGx consortium received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 668353. The DPWG received funding from the Royal Dutch Pharmacists Association. Publisher Copyright: © 2022, The Author(s), under exclusive licence to European Society of Human Genetics.

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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.

KW - Colorectal-cancer

KW - Efficacy

KW - Japanese

KW - Neutropenia

KW - Polymorphisms

KW - Risk

KW - Safety

KW - Ugt1a1-asterisk-28 genotype

KW - Variants

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SP - 982

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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

Bibliographical note

UN SDGs

Keywords

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