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Capecitabine Pharmacogenetics: Historical Milestones and Progress toward Clinical Implementation. (Pharmacogenomics, Oct 2016)

Syn N1,2,3, Lee SC1,2, Goh BC1,2,3, Yong WP1,2

1Department of Haematology-Oncology, National University Cancer Institute, Singapore 119228.
2Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599.
3Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600.

Abstract:

The third-generation, orally-available fluoropyrimidine capecitabine (Xeloda™, Hoffmann-La Roche, Basel, Switzerland) has approved indications for the front-line therapy of advanced and/or metastatic colorectal cancer and pretreated metastatic breast cancer. Being a 5-fluorouracil prodrug, it has also increasingly substituted infusional fluorouracil as the fluoropyrimidine backbone in chemotherapy regimens for advanced esophagogastric malignancies on the basis of equivalent efficacy and its convenient outpatient oral dosing schedule [1–3]. Despite the proven efficacy and tolerability profile of capecitabine, selection of an optimal starting dosage remains a challenge, and clinical practices for treatment initiation differ worldwide [4]. Stark interindividual and inter-regional heterogeneity exists with respect to toxicity and efficacy profiles, and may be partially explained by genetic variation, with the most well-established pharmacogenes to-date being DPYD and TYMS. In this Editorial, we highlight several historical milestones and recent progress that have added to the evidence base for clinical implementation of pharmacogenetics-guided capecitabine dosing.

KEYWORDS: DPYD; TYMS; Xeloda; capecitabine; fluoropyrimidines; hand–foot syndrome; pharmacogenetics; ­thymidylate synthase

PMID: 27676641