An update to the CPIC dosing guidelines for DPYD and fluoropyrimidines has recently been added to the CPIC and PharmGKB websites.
The most recent version of the guideline, published in Clinical Pharmacology & Therapeutics in November 2017, recommended that patients who were DPYD intermediate metabolizers with an activity score of 1 have a dose reduction of 50%, while those with an activity score of 1.5 have a dose reduction of 25%-50%. At the time of guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing for an activity score of 1.5.
However, a recent study in The Lancet Oncology by Henricks et al. found evidence supporting a dose reduction of 50% in individuals with an activity score of 1.5 (more on this paper can be found in a related PharmGKB blogpost). Upon consideration of this new data, CPIC revised its recommendation such that all DPYD intermediate metabolizers, both those with an activity score of 1 and those with an activity score of 1.5, should receive a 50% dose reduction.
An update was also made noting that patients homozygous for the 2846A>T variant may require a dose reduction of greater than 50%. The full update can be read on the CPIC website, as well as on the PharmGKB pages for capecitabine and fluorouracil.
Read the update and the original guideline on the CPIC website
Read the update and the original guideline on the PharmGKB website (capecitabine; fluorouracil)
Read the paper by Henricks et al. in The Lancet Oncology
Read the PharmGKB blogpost on the Henricks et al. paper