1. Clinical implementation of pre-treatment DPYD genotyping in capecitabine-treated metastatic breast cancer patients
- Author
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Chara Stavraka, Janine Mansi, Karen DeSouza, Anthony M. Marinaki, E. Karapanagiotou, Matthaios Kapiris, Athanasios Pouptsis, Leroy Okonta, Dionysis Papadatos-Pastos, and Philip Charlton
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,VARIANTS ,FLUOROPYRIMIDINE THERAPY ,TOXICITY ,FLUOROURACIL PLUS LEUCOVORIN ,COLORECTAL-CANCER ,0302 clinical medicine ,ORAL CAPECITABINE ,Neoplasm Metastasis ,Aged, 80 and over ,DPYD screening ,Brief Report ,Medical record ,Middle Aged ,Metastatic breast cancer ,SAFETY ,030220 oncology & carcinogenesis ,5-FLUOROURACIL ,Female ,Fluorouracil ,Life Sciences & Biomedicine ,medicine.drug ,Adult ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,Genotype ,Breast Neoplasms ,Breast Neoplasms, Male ,Capecitabine ,03 medical and health sciences ,Breast cancer ,Internal medicine ,medicine ,Dihydropyrimidine dehydrogenase ,Humans ,1112 Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,DPYD genotyping ,Genotyping ,Dihydrouracil Dehydrogenase (NADP) ,Aged ,Retrospective Studies ,Science & Technology ,Polymorphism, Genetic ,PHARMACOGENETICS ,business.industry ,Fluoropyrimidines ,1103 Clinical Sciences ,Retrospective cohort study ,medicine.disease ,DIHYDROPYRIMIDINE DEHYDROGENASE ,030104 developmental biology ,Toxicities ,DPYD ,business - Abstract
Purpose Metastatic breast cancer (mBC) patients with DPYD genetic variants linked to loss of dihydropyrimidine dehydrogenase (DPD) activity are at risk of severe capecitabine-associated toxicities. However, prospective DPYD genotyping has not yet been implemented in routine clinical practice. Following a previous internal review in which two patients underwent lengthy hospitalisations whilst receiving capecitabine, and were subsequently found to be DPD deficient, we initiated routine DPYD genotyping prior to starting capecitabine. This study evaluates the clinical application of routine DPYD screening at a large cancer centre in London. Methods We reviewed medical records for consecutive patients with mBC who underwent DPYD genotyping before commencing capecitabine between December 2014 and December 2017. Patients were tested for four DPYD variants associated with reduced DPD activity. Results Sixty-six patients underwent DPYD testing. Five (8.4%) patients were found to carry DPYD genetic polymorphisms associated with reduced DPD activity; of these, two received dose-reduced capecitabine. Of the 61 patients with DPYD wild-type, 14 (23%) experienced grade 3 toxicities which involved palmar–plantar erythrodysesthesia (65%), and gastrointestinal toxicities (35%); no patient was hospitalised due to toxicity. Conclusions Prospective DPYD genotyping can be successfully implemented in routine clinical practice and can reduce the risk of severe fluoropyrimidine toxicities.
- Published
- 2019
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