Page 34 - Read Online

Page 56 Olivera et al. Cancer Drug Resist 2019;2:53-68 I http://dx.doi.org/10.20517/cdr.2018.25

Table 1. Summary of the recommendations provided in CPIC and DPWG guidelines for drugs employed in oncology
Reference Risk
Drug Gene SNP genotype genotype Guideline recommendation
Azathioprine, CPIC [17-19]
Mercaptopurine,
Thioguanine #
TPMT rs1800462 CC CG, GG Any Heterozygote, including 1/*3A (both risk variants
rs1800584 CC CT, TT located in the same allele): Consider a reduction starting
rs1142345 TT TC, CC at 30%-80% of the normal starting dose (if normal
2
rs1800460 CC CT, TT starting dose is equal or higher than 75 mg/m /day, or
equal or higher than 1.5 mg/kg/day in Mercaptopurine,
and 2-3 mg/kg/day in Azathioprine). In the case of
Thioguanine, start with 50%-80% of normal dose if it is
2
equal or higher than 40-60 mg/m /day. Allow 2-4 weeks
to reach steady state after each dose adjustment
Any Homozygote, plus multiple heterozygotes in *2, *3B
and *4, that is an individual carrying two non functional
alleles: Consider alternative agents. If not possible,
start with a daily dose reduction 10 times and three
times a week. Adjust the dose according to the degree
of myelosuppression and the specific patterns of the
disease. Allow 4-6 weeks to reach a steady state after
each dose adjustment
NUDT15 rs116855232 CC CT, TT For CT follow the same recommendation as for
Heterozygotes in TPMT. For TT, follow the same
recommendation as for TPMT Homozygotes, except for
Thioguanine, where the reduction should be to 25%
DPWG [6]
Any Heterozygote: Select alternative drug or reduce
dose by 50%. Increase dose in response of hematologic
monitoring efficacy
Homozygotes or combination of two or more
Heterozygotes: Select alternative drug or reduce dose
by 90%. Increase dose in response of hematologic
monitoring efficacy
Capecitabine, CPIC/DPWG [6,20,21]
Fluorouracil # Other variants are included in the DPWG guideline, but
they are extremely rare [6]
DPYD rs3918290 CC CT, TT CT: Reduce dose by 50%. TT: Change to alternative
agents
rs55886062 AA AC, CC AC: Reduce dose by 50%. CC: Change to alternative
agents
rs3918290+ CC + AA CT, TT + AC, CC Change to alternative agents
rs55886062
rs67376798 TT AT, AA Reduce dose by 50%
rs67376798+ TT + CC AT, AA + CT, TT Change to alternative agents
rs3918290
rs67376798+ TT + AA AT, AA + AC, CC Change to alternative agents
rs55886062
rs75017182 GG CG, CC Reduce dose by 50%.
rs75017182+ GG + CC CG, CC + CT, TT Change to alternative agents
rs3918290
rs75017182+ GG + AA CG, CC + AC, CC Change to alternative agents
rs55886062
Tegafur DPWG [6]
DPYD rs3918290 CC CT, TT Homozygotes for any Risk genotype or combination of
two heterozygotes: select alternative drug. Fluorouracil or
capecitabine are not suitable alternatives because both
are also metabolized by DPD. Other variants are included
[6]
in the guideline, but they are extremely rare . Tegafur has
no longer recommendations from CPIC based on DPYD
genotype. This is due to limited evidence regarding the
impact of DPYD variants on tegafur toxicity risk
rs72549303 G/G G/del, del/del
rs72549309 ATGA/ATGA ATGA/del, del/del

rs1801266 GG AG, AA
rs72549306 CC AC, AA