Review

. 2023 Mar:181:3-17.

doi: 10.1016/j.ejca.2022.11.028. Epub 2022 Dec 9.

Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency

Affiliations

¹ Laboratory of Oncopharmacology, Centre Antoine Lacassagne, Nice, France.
² Department of Clinical Chemistry, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, F-75006 Paris, France.
³ Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France.
⁴ SMARTc, CRCM INSERM U1068, Université Aix-Marseille, Marseille, France; Laboratory of Pharmacokinetics and Toxicology, Hôpital Universitaire La Timone, F-13385 Marseille, France; COMPO, CRCM INSERM U1068-Inria, Université Aix-Marseille, Marseille, France.
⁵ Regional Center of Pharmacovigilance, Department of Pharmacology, Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Université de Paris, Paris, France; French Pharmacovigilance Network, France.
⁶ Laboratory of Biochemistry and Molecular Biology, Centre Hospitalo-uinversitaire de Tours, Tours, France; INSERM U1248, IPPRITT, University of Limoges, Limoges, France.
⁷ Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris University; Assistance Publique-Hôpitaux de Paris, Paris, France.
⁸ SIRIC CARPEM, Université de Paris; Fédération Francophone de Cancérologie Digestive (FFCD), Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France.
⁹ Laboratory of Pharmacology, Institut Claudius Regaud, IUCT-Oncopole and CRCT, INSERM UMR1037, Université Paul Sabatier, Toulouse, France.
¹⁰ Department of Clinical Chemistry, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, F-75006 Paris, France. Electronic address: marie-anne.loriot@aphp.fr.

PMID: 36621118
DOI: 10.1016/j.ejca.2022.11.028

Review

Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency

Marie-Christine Etienne-Grimaldi et al. Eur J Cancer. 2023 Mar.

. 2023 Mar:181:3-17.

doi: 10.1016/j.ejca.2022.11.028. Epub 2022 Dec 9.

Affiliations

¹ Laboratory of Oncopharmacology, Centre Antoine Lacassagne, Nice, France.
² Department of Clinical Chemistry, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, F-75006 Paris, France.
³ Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France.
⁴ SMARTc, CRCM INSERM U1068, Université Aix-Marseille, Marseille, France; Laboratory of Pharmacokinetics and Toxicology, Hôpital Universitaire La Timone, F-13385 Marseille, France; COMPO, CRCM INSERM U1068-Inria, Université Aix-Marseille, Marseille, France.
⁵ Regional Center of Pharmacovigilance, Department of Pharmacology, Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Université de Paris, Paris, France; French Pharmacovigilance Network, France.
⁶ Laboratory of Biochemistry and Molecular Biology, Centre Hospitalo-uinversitaire de Tours, Tours, France; INSERM U1248, IPPRITT, University of Limoges, Limoges, France.
⁷ Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris University; Assistance Publique-Hôpitaux de Paris, Paris, France.
⁸ SIRIC CARPEM, Université de Paris; Fédération Francophone de Cancérologie Digestive (FFCD), Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France.
⁹ Laboratory of Pharmacology, Institut Claudius Regaud, IUCT-Oncopole and CRCT, INSERM UMR1037, Université Paul Sabatier, Toulouse, France.
¹⁰ Department of Clinical Chemistry, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, F-75006 Paris, France. Electronic address: marie-anne.loriot@aphp.fr.

PMID: 36621118
DOI: 10.1016/j.ejca.2022.11.028

Abstract

Fluoropyrimidine drugs (FP) are the backbone of many chemotherapy protocols for treating solid tumours. The rate-limiting step of fluoropyrimidine catabolism is dihydropyrimidine dehydrogenase (DPD), and deficiency in DPD activity can result in severe and even fatal toxicity. In this review, we survey the evidence-based pharmacogenetics and therapeutic recommendations regarding DPYD (the gene encoding DPD) genotyping and DPD phenotyping to prevent toxicity and optimize dosing adaptation before FP administration. The French experience of mandatory DPD-deficiency screening prior to initiating FP is discussed.

Keywords: 5-Fluorouracile; DPD; DPYD; Dihydropyrimidine dehydrogenase; Drug toxicity; Fluoropyrimidine; Genotyping; Guidelines; Pharmacogenetics; Phenotyping.

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Conflict of interest statement

Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency

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Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency

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