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. 2020 Dec;16(12):793-798.
doi: 10.1200/OP.20.00553. Epub 2020 Nov 16.

All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide

Federico Innocenti  1 , Sarah C Mills  1 , Hanna Sanoff  2 , Joseph Ciccolini  3 , Heinz-Josef Lenz  4 , Gerard Milano  5
Affiliations

All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide

Federico Innocenti et al. JCO Oncol Pract. 2020 Dec.

Abstract

Fluoropyrimidines (fluorouracil, capecitabine, and other analogs) are highly used anticancer drugs worldwide. However, patients with cancer treated with these drugs might experience severe, life-threatening toxicity because of germline genetic variation in the DPYD gene. This is a genetic predisposition with an established mechanistic basis that links genetic variation in the DPYD gene to an increase in systemic drug exposure, resulting in an increased risk of toxicity. Pharmacology guidelines provide recommendations on avoiding treatment with fluoropyrimidines or reducing their dose in patients carrying DPYD genetic variants conferring an increased risk of toxicity. However, oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending genetic testing. In this scenario of contradicting information, practicing oncologists struggle with reaching an informed decision on whether genetic testing should be applied before treatment. This is mostly due to uncertainty about the clinical relevance of genetic testing from the perspective of a practicing oncologist. To reach an informed decision, practicing oncologists need access to concise information on the genetic variants to be tested and a practitioner-friendly interpretation of the test results. We believe this information is currently lacking. To our knowledge, for the first time, we provide a single guide for health care professionals to make an evidence-based decision about DPYD testing for patients with cancer. This article provides the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for DPYD. This document assists practitioners in quickly evaluating whether, when, where, and how to order a DPYD genetic test.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Federico Innocenti

Consulting or Advisory Role: Symberix, Emerald Lake Safety

Patents, Royalties, Other Intellectual Property: United States Provisional Application: ”Methods of identifying risk of bevacizumab-induced proteinuria and hypertension,” Innocenti F, Quintanilha J, Lin D, Owzar K, Wang J. Filed on September 20, 2019, serial number 62/903,442. United States Patent: “Flavopiridol drug combinations and methods with reduced side effects,” Ratain MJ, Innocenti F, Iyer L. Filed on April 12, 2001, serial number 09/835,082. United States Patent: “Optimization of cancer treatment with irinotecan,” Ratain MJ, Innocenti F, Karabatsos P, Grimsley C, Di Rienzo A. Filed on February 12, 2003, serial number 60/446,942

Hanna Sanoff

Research Funding: Bayer (Inst)

Joseph Ciccolini

Honoraria: Genentech (Inst)

Travel, Accommodations, Expenses: Roche

Heinz-Josef Lenz

Honoraria: Merck Serono, Roche, Bayer, Boehringer Ingelheim, Isofol, GSK

Consulting or Advisory Role: Merck Serono, Roche, Bayer, BMS, GSK

Travel, Accommodations, Expenses: Merck Serono, Bayer

Gerard Milano

Honoraria: BMS, Merck, Servier, Pierre Fabre Oncology

No other potential conflicts of interest were reported.

Comment in

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