Relationship between UGT1A1*6/*28 polymorphisms and severe toxicities in Chinese patients with pancreatic or biliary tract cancer treated with irinotecan-containing regimens

Figures & data

Table 1 Patient characteristics

Characteristics	n	%
Age (years)
≤60	26	54.2
>60	22	25.8
Sex
Male	25	52.1
Female	23	47.9
ECOG
0	33	68.7
1	15	31.3
Location of primary tumor
Pancreatic cancer	36	75.0
Biliary tract cancer	12	25.0
Extent of disease
Locally advanced	27	56.2
Metastatic	21	43.8
Biliary drainage
Endoscopic drainage	16	33.3
Percutaneous drainage	4	8.3
Line of treatment
Second line	36	75.0
Third line	12	25.0
Prior first-line chemotherapy
Gemcitabine	4	8.3
Gemcitabine + oxaliplatin	28	58.4
Gemcitabine + cisplatin	12	25.0
Gemcitabine + nab-paclitaxel	4	8.3
Prior second-line chemotherapy
S-1	2	4.2
S-1 + oxaliplatin	10	20.8
Current treatment
FOLFIRI	33	68.7
Irinotecan monotherapy	15	31.3

Abbreviations: ECOG, Eastern Cooperative Oncology Group; FOLFIRI, a chemotherapy regimen containing folinic acid (FOL), fluorouracil (F), and irinotecan (IRI).

Table 2 Genotyping of UGT1A1*6/*28 in 48 patients

Genotyping	n	%
UGT1A1*6
GG	34	70.8
GA	12	25.0
AA	2	4.2
UGT1A1*28
TA6/TA6	38	79.2
TA6/TA7	9	18.8
TA7/TA7	1	2.0
UGT1A1*6 and UGT1A1*28
GG and TA6/TA6	24	50.0
GG and TA6/TA7	9	18.8
GG and TA7/TA7	1	2.0
GA and TA6/TA6	12	25.0
GA and TA6/TA7	0	0.0
GA and TA7/TA7	0	0.0
AA and TA6/TA6	2	4.2
AA and TA6/TA7	0	0.0
AA and TA7/TA7	0	0.0

Table 3 Relationship between clinical characteristics and irinotecan-related toxicities

Characteristics	Neutropenia grade, n (%)		P-value	Diarrhea grade, n (%)		P-value
	0–II	III–IV		0–II	III–IV
Age (years)
≤60	14 (29.2)	12 (25.0)	0.961	23 (47.9)	3 (6.3)	1.000
>60	12 (25.0)	10 (20.8)		19 (39.5)	3 (6.3)
Sex
Male	12 (25.0)	13 (27.1)	0.371	22 (45.7)	3 (6.3)	1.000
Female	14 (29.2)	9 (18.8)		20 (41.7)	3 (6.3)
ECOG
0	18 (37.5)	15 (31.2)	0.938	29 (60.4)	4 (8.3)	1.000
1	8 (16.7)	7 (14.6)		13 (27.1)	2 (4.2)
Line of treatment
Second line	20 (41.7)	16 (33.3)	0.738	32 (66.7)	4 (8.3)	0.631
Third line	6 (12.5)	6 (12.5)		10 (20.8)	2 (4.2)
Current treatment
FOLFIRI	15 (31.2)	18 (37.5)	0.072	30 (62.4)	3 (6.3)	0.360
Irinotecan monotherapy	11 (22.9)	4 (8.3)		12 (25.0)	3 (6.3)

Abbreviations: ECOG, Eastern Cooperative Oncology Group; FOLFIRI, a chemotherapy regimen containing folinic acid (FOL), fluorouracil (F), and irinotecan (IRI).

Table 4 Relationship between UGT1A1*6/*28 polymorphisms and neutropenia

Genotyping	Neutropenia grade, n (%)		P-value
	0–II	III–IV
UGT1A1*6
GG	22 (64.7)	12 (35.3)	0.022
GA or AA	4 (28.6)	10 (71.4)
UGT1A1*28
TA6/TA6	22 (57.9)	16 (42.1)	0.312
TA6/TA7 or TA7/TA7	4 (40.0)	6 (60.0)
UGT1A1*6/*28
Double wild-type	18 (75.0)	6 (25.0)	0.004
Heterozygous variant type	8 (38.1)	13 (61.9)
Homozygous variant type	0 (0.0)	3 (100.0)

Figure S1 Examples of sequencing chromatograms of UGT1A1*6/*28 polymorphisms.