Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

152 Applying Pharmacogenomics in Therapeutics
TABLE 6.3
Clinical Recommendations for Biomarkers Related to
Drug-Metabolizing Enzymes
PGx Biomarkers/
Affected Cancer
Drugs
UGT1A1/
Irinotecan
Nilotinib
DPD/
Fluorouracil (5-FU)
Capecitabine
TPMT/
6-Mercaptopurine
(6-MP)
CYP2D6/
Tamoxifen
CYP2B6/
Cyclophosphamide
Ifosfamide
MTHFR
Methotrexate
Clinical
Significant
Polymorphisms Genetic Testing Clinical Recommendations
UGT1A1*28
(insertion of an
additional
seventh TA)
sequence in the
promoter
region of UGT
1A1 gene. 25
UGT1A1 Gene
Polymorphism
(TA Repeat)
testing by PCR
A reduction in the starting dose of
irinotecan for any patient
homozygous for the
UGT1A1*28 allele. 24
Routine use of genotyping when
dosing irinotecan at high dose
(>200 mg/m 2 ) may be useful. 26
The FDA recommends, but does
not require, genetic testing for
UGT1A1 variants prior to
initiating or reinitiating
treatment with nilotinib but
recommends frequent liver
function monitoring. 27
DPD*2A Amplichip Genetic screening recommended
to be performed before starting
5-FU therapy. 28,29
TPMT*2 TPMT Activity Substantial dose reductions are
TPMT*3A Assay
generally required for
TPMT*3C 30
homozygous TPMT-deficient
patients. 31
CYP2D6*3
CYP2D6*4
CYP2D6*5
CYP2D6*6 32
CYP2B6*5
CYP2B6*6
C677T
AmpliChip
CYP450 Test 33
Pyrosequencing
assays for
CYP2B6
polymorphisms 35
Methotrexate
sensitivity 2
Mutations assay
(ARIP lab)
No clinical recommendations
regarding CYP2D6
polymorphisms and tamoxifen
therapy. 34
CYP2B6 is highly inducible. The
interindividual difference of
CYP2B6 enzyme activity can be
20- to 250-fold, which can
affect drug efficacy and
toxicity. 36
C677T homozygous variant with
35% of normal enzyme activity
occurs in up to 10% of whites.
The rate of oral mucositis is
36% higher for chronic
myelogenous leukemia patients
with the C677T polymorphism
than those without. 37,38
(Continued)