A case report of a severe fluoropyrimidine-related toxicity due to an uncommon DPYD variant.

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From: Medicine(Vol. 98, Issue 18)
Publisher: Lippincott Williams & Wilkins, WK Health
Document Type: Article
Length: 641 words

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Byline: Vincenzo De Falco, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Maria Iole Natalicchio, Laboratorio di Biologia Molecolare, Ospedale Riuniti, Foggia, Italia; Stefania Napolitano, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Nicola Coppola, Malattie Infettive, Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, UniversitÈá degli Studi della Campania Luigi Vanvitelli; Giovanni Conzo, UOC di Chirurgia Generale ed Oncologica, UniversitÈá degli Studi della Campania Luigi Vanvitelli; Erika Martinelli, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Nicoletta Zanaletti, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Pasquale Vitale, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Emilio Francesco Giunta, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Maria Teresa Vietri, UOC Patologia clinica e molecolare, Dipartimento di Medicina di Precisione, DAI dei Sevizi di laboratorio e SanitÈá pubblica, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Complesso di S. Andrea delle Dame, Napoli, Italia.; Pietro Paolo Vitiello, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Davide Ciardiello, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Anna Marinaccio, Laboratorio di Biologia Molecolare, Ospedale Riuniti, Foggia, Italia; Ferdinando De Vita, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Fortunato Ciardiello, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli; Teresa Troiani, Oncologia Medica, Dipartimento di Medicina di Precisione, UniversitÈá degli Studi della Campania Luigi Vanvitelli, Napoli Abstract INTRODUCTION: Fluoropyrimidines such as 5-fluorouracil (5-FU) and its orally active prodrug, capecitabine, are widely used in the treatment of gastrointestinal cancer, including colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) plays an important role in the 5-FU metabolism. Dihydropyrimidine dehydrogenase gene (DPYD) is a highly polymorphic gene with several hundreds of reported genetic variants and DPD activity levels vary considerably among individuals, with different 5-FU-related efficacy and toxicity. About 5% of the population is deficient in DPD enzyme activity. The most well studied DPYD variant is the IVS14+1G A, also known as DPYD êù2A. In this report, we present a case of a patient with a double heterozygote DPYD variant (DPYD activity score: 0,5 according to Clinical Pharmacogenetics Implementation Consortium) who experienced a severe fluoropyrimidine-related toxicity resolved without any consequence. PATIENT CONCERNS: A 46-years-old Caucasian man with diagnosis of left colon adenocarcinoma underwent left hemicolectomy on July 2017: pT3 G3 N1c M0. According to the disease stage, he started an adjuvant therapy with XELOX using capecitabine at 50% of total dose, because of his DPYD IVS14+1G A variant, detected before the treatment. DIAGNOSIS: After few days, despite of this dose reduction, he experienced life-threatening adverse events such as mucositis G3, diarrhea G3, neutropenia G4, thrombocytopenia G4, and hyperbilirubinemia G3 according to Common Terminology Criteria for Adverse Events v 5.0. INTERVENTIONS: As first, we set up an intensive rehydration therapy, antibiotic and antifungal prophylaxis, Granulocyte-Colony Stimulating Factors, and supportive blood transfusions. Additional genetic tests revealed a double heterozygote variant of DPYD gene (DPYD IVS14+1G A and 2846A T) which is a very rare situation and only 3 cases are described in literature, all of them concluded with patient's death. OUTCOMES: After 3 weeks of intensive therapy, the patient was fully recovered. Furthermore, all the whole-body CT scans performed since discharge from the hospital until now, have confirmed no evidence of disease. CONCLUSIONS: Recent studies demonstrated that screening strategy for the most common DPYD variants allowed for avoiding toxicities and saving money. This report underlines the importance of genotyping DPYD before treatment and emphasizes the role of genotype-guided dose individualization.

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Gale Document Number: GALE|A671688084