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. 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.
['Stavraka|Chara|C|http://orcid.org/0000-0001-7623-299X', 'Pouptsis|Athanasios|A|', 'Okonta|Leroy|L|', 'DeSouza|Karen|K|', 'Charlton|Philip|P|', 'Kapiris|Matthaios|M|', 'Marinaki|Anthony|A|', 'Karapanagiotou|Eleni|E|', 'Papadatos-Pastos|Dionysis|D|', 'Mansi|Janine|J|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000964:Antimetabolites, Antineoplastic D001943:Breast Neoplasms D018567:Breast Neoplasms, Male D000069287:Capecitabine D042943:Dihydrouracil Dehydrogenase (NADP) D005260:Female D005472:Fluorouracil D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D009362:Neoplasm Metastasis D011110:Polymorphism, Genetic D012189:Retrospective Studies
DPYD genotyping Metastatic breast cancer Toxicities Capecitabine DPYD screening Fluoropyrimidines