Clinical implementation of pre-treatment DPYD genotyping in capecitabine-treated metastatic breast cancer patients

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. Follow...

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Published in:Breast cancer research and treatment 2019-06, Vol.175 (2), p.511-517
Main Authors: Stavraka, Chara, Pouptsis, Athanasios, Okonta, Leroy, DeSouza, Karen, Charlton, Philip, Kapiris, Matthaios, Marinaki, Anthony, Karapanagiotou, Eleni, Papadatos-Pastos, Dionysis, Mansi, Janine
Format: Article
Language:English
Subjects:
Breast cancer
Brief Report
Cancer
Cancer patients
Cancer research
Cancer therapies
Care and treatment
Clinical medicine
Genetic aspects
Genetic diversity
Genetic polymorphisms
Genotyping
Medical records
Medicine
Medicine & Public Health
Metastases
Metastasis
Oncology
Oncology, Experimental
Patients
Toxicity
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Summary: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.
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-019-05144-9