Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy

Table 1 Demographic and clinical characteristics of the patients n (%)

Characteristics	Value
Total	120 (100)
Age, yr
mean ± SD	49.6 ± 10.5
Median (range)	18-72
Gender
Male	71 (59.2)
Female	49 (40.8)
KPS
≥ 80%	96 (80.0)
70%	20 (16.7)
60%	4 (3.3)
Primary tumor
Right-sided	33 (27.5)
Left-sided	87 (72.5)
Histology
Glandular	89 (74.2)
Mucinous	13 (10.8)
Signet-ring cell	3 (2.5)
Mixed	10 (8.3)
Unfixed	5 (4.2)
First-line chemotherapy
FOLFIRI	109 (90.8)
mXELIRI	7 (5.8)
Irinotecan	4 (3.3)
Serum total bilirubin, μmol/L
mean ± SD	10.2 ± 4.3
Range	3.1-26.9
Serum unconjugated bilirubin, μmol/L
mean ± SD	7.2 ± 3.1
Range	2.5-19.2
UGT1A1*28 genotype1
(TA)6/6	84 (70.0)
(TA)6/7	34 (28.3)
(TA)7/7	2 (1.7)

¹Variants were in Hardy-Weinberg equilibrium (P > 0.05). KPS: Karnofsky performance status.

Table 2 Demographic and clinical characteristics between patients with objective response and patients without objective response n (%)

Characteristics	Objective response		P value	P value1
	No	Yes
Age, yr (mean ± SD)	48.2 ± 10.9	52.1 ± 9.0	0.0472	0.066
Gender
Male	44 (62.0)	27 (38.0)	0.4023	0.492
Female	34 (69.4)	15 (30.6)
KPS
≥ 80%	64 (66.7)	32 (33.3)	0.4443	0.42
< 80%	14 (58.3)	10 (41.7)
Primary tumor
Right-sided	22 (66.7)	11 (33.3)	0.8143	0.885
Left-sided	56 (64.4)	31 (35.6)
Histology
Glandular	55 (61.8)	34 (38.2)	0.2133	0.407
Other	23 (74.2)	8 (25.8)
First-line chemotherapy
FOLFIRI	71 (65.1)	38 (34.9)	0.8824	0.832
mXELIRI	4 (57.1)	3 (42.9)
Irinotecan	3 (75.0)	1 (25.0)

¹P-values were adjusted for age, sex, KPS, primary tumor site, histology and treatment regimen in logistic regression models;

²P-value was calculated using two-sided t tests;

³P-values were calculated using two-sided χ² tests;

⁴P-value was calculated using Fisher’ exact tests. KPS: Karnofsky performance status.

Table 3 Association between UGT1A1*28 genotypes and response to treatment n (%)

UGT1A1*28 genotype	Complete response	Partial response	Stable disease	Progressive disease	Objective response2		Simple analysis			Multiple analysis3
					n	Yes	OR	95%CI	P value	OR	95%CI	P value
(TA)6/6	3 (3.6)	33 (39.3)	34 (40.5)	14 (16.7)	84	36 (42.9)	1.000 (ref.)			1.000 (ref.)
(TA)6/7 or (TA)7/71	1 (2.8)	5 (13.9)	18 (50.0)	12 (33.3)	36	6 (16.7)	0.267	0.100-0.709	0.008	0.244	0.088-0.678	0.007

¹In the dominant model;

²Yes, partial and complete response;

³Multiple analyses were adjusted for age, sex, KPS, histology, primary tumor site and treatment regimen. KPS: Karnofsky performance status.

Table 4 Association between serum total/unconjugated bilirubin levels and response to treatment

	Objective response1		Simple analysis		Multiple analysis2
	n	Yes (%)	OR (95%CI)	P value	OR (95%CI)	P value
Serum total bilirubin
> 13.0	24	4 (16.7)	1.000 (ref.)		1.000 (ref.)
≤ 13.0	96	38 (39.6)	3.276 (1.038-10.333)	0.043	3.874 (1.127-13.319)	0.032
Serum unconjugated bilirubin
> 4.1	107	33 (30.8)	1.000 (ref.)		1.000 (ref.)
≤ 4.1	13	9 (69.2)	5.045 (1.450-17.561)	0.011	5.923 (1.561-22.479)	0.009

¹Yes, partial and complete response;

²Multiple analyses were adjusted for age, sex, KPS, histology, primary tumor site and treatment regimen. KPS: Karnofsky performance status.

Table 5 Association between combined bilirubin levels and response to treatment

Combined bilirubin levels1	Objective response2		Simple analysis		Multiple analysis3
	n	Yes (%)	OR (95%CI)	P value	OR (95%CI)	P value
Group 1	24	4 (16.7)	1.000 (ref.)		1.000 (ref.)
Group 2	83	29 (34.9)	2.685 (0.838-8.604)	0.096	3.215 (0.918-11.255)	0.068
Group 3	13	9 (69.2)	11.250 (2.286-55.367)	0.003	16.001 (2.802-91.371)	0.002

¹Group 1: individuals with total bilirubin > 13.0 and unconjugated bilirubin > 4.1; Group 2: individuals with total bilirubin ≤ 13.0 and unconjugated bilirubin > 4.1; Group 3: individuals with total bilirubin ≤ 13.0 and unconjugated bilirubin ≤ 4.1;

²Yes, partial and complete response;

³Multiple analyses were adjusted for age, sex, KPS, histology, primary tumor site and treatment regimen; KPS: Karnofsky performance status.