Pharmacogenomics guided dosing for fluoropyrimidine and irinotecan chemotherapies for patients with cancer (PACIFIC-PGx): study protocol of a multicentre clinical trial

Figures & data

Table 1. DPYD variants tested as part of the trial and activity score.

rsID	Nucleotide change	Allele functional status	Activity score
rs3918290	c.1905 + 1G > A	No function	0
rs55886062	c.1679T > G	No function	0
rs67376798	c.2846A > T	Decreased function	0.5
rs56038477 (rs75017182, rs56276561)	c.1236G > A (c.1129–5923C > G, c.483 + 18G > A)	Decreased function	0.5
rs115232898	c.557A > G^(additional variant tested as part of the trial and commonly observed in the African ancestry as per CPIC)	Decreased function	0.5

Table 2. DPYD and UGT1A1 genotyping dose recommendations.

DPYD normal metaboliser	No dose adjustments are required.
DPYD intermediate metaboliser	Reduce starting dose by 50% in the first 2 cycles followed by titration of dose based on toxicity.
DPYD poor metaboliser	Avoid use of 5-FU or capecitabine based regimens in this patient.
UGT1A1*1/*1	No dose adjustments are required.
Normal metaboliser
UGT1A1 *1/*28	No dose adjustments are required.
Intermediate metaboliser
UGT1A1 *28/*28	Reduce starting dose by 30% at cycle 1, followed by titration of dose based on neutrophil count.
Poor metaboliser