Efficacy Analysis of Adjuvant Chemotherapy with Gemcitabine Plus Platinum or S-1 in Biliary Tract Carcinoma: A Multi-Center Retrospective Study

Figures & data

Table 1 Clinicopathological Characteristics of 136 Patients Enrolled

Clinicopathological Features	GP/GEMOX (n =81)	GS (n =55)	P value
Gender			0.941
Male	27(33%)	18(33%)
Female	54(67%)	37(67%)
Age			0.600
≤58	42(52%)	26(47%)
>58	39(48%)	29(53%)
>65*	9(11%)	11(20%)	0.151
ECOG PS			0.343
0	33(41%)	18(33%)
1	48(59%)	37(67%)
Comorbidity			0.561
No	54(67%)	34(62%)
Yes	27(33%)	21(38%)
Tumor site			0.710
Gallbladder	46(57%)	33(60%)
Bile duct	35(43%)	22(40%)
TNM-stage			0.461
I–II	30(37%)	17(31%)
III–IVA	51(63%)	38(69%)
T-stage			0.284
T1-T2	26(32%)	13(24%)
T3-T4	55(68%)	42(76%)
Lymph node			0.667
N-	53(65%)	34(62%)
N+	28(35%)	21(38%)
Pathological differentiation			0.803
Well-moderately	46(57%)	32(58%)
Poor	27(33%)	16(29%)
Unknown	8(10%)	7(13%)
Chemotherapy cycles			0.464
<6	42(52%)	25(45%)
6–8	39(48%)	30(55%)

Note: *Considering the toxicity of platinoids, it was also compared in elderly patients over 65 years old.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; GP, gemcitabine plus cisplatin; GEMOX, gemcitabine plus oxaliplatin; GS, gemcitabine plus S-1; N-, lymph node negative; N+, lymph node negative.

Figure 1 Flow chart of patient enrolment.

Table 2 Univariate Analysis of Clinicopathological Factors Associated with RFS

Clinicopathological Features	mRFS (Month,95% CI)	P value
Gender		0.330
Male	21.0(8.3–33.7)
Female	14.1(8.3–20.0)
Age		0.769
≤58	19.1(9.8–28.4)
>58	15.6(7.5–23.7)
ECOG PS		0.215
0	26.9(11.2–42.6)
1	15.6(9.4–21.8)
Comorbidity		0.254
No	24.3(4.7–43.9)
Yes	15.8(9.8–21.8)
Tumor site		0.945
Gallbladder	15.9(8.8–23.0)
Bile duct	18.9(9.9–27.9)
TNM-stage		0.071
I–II	26.9(6.5–47.3)
III–IVA	13.0(5.9–20.1)
T-stage		0.167
T1-T2	37.9(15.2–60.7)
T3-T4	15.6(9.9–21.3)
Lymph node		0.013
N-	30.8(14.3–47.3)
N+	10.8(4.9–16.7)
Pathological differentiation		0.471
Well-moderately	24.3(16.2–32.4)
Poor	8.7(3.5–13.9)
Unknown	15.9(12.7–19.1)
Chemotherapy cycles		0.036
<6	9.5(3.9–15.1)
6–8	24.5(9.4–39.6)
Chemotherapy regimen		0.092
GP/GEMOX	14.1(6.7–21.5)
GS	33.0(9.3–56.7)
Baseline CA19-9		0.001
≤39 U/mL	19.1(16.1–22.1)
>39 U/mL	6.6(3.4–9.8)
CA19-9 doubled after 2 cycles chemotherapy		0.021
Yes	5.9(2.3–12.9)
No	19.1(15.6–22.6)

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; GP, gemcitabine plus cisplatin; GEMOX, gemcitabine plus oxaliplatin; GS, gemcitabine plus S-1; N-, lymph node negative; N+, lymph node negative; mRFS, median relapse-free survival.

Table 3 Multivariate Cox Proportional Hazards Model of RFS

Variables		HR	95% CI	P value
Gender	Male vs female	0.764	0.441–1.323	0.337
Age	≤58 vs >58	1.235	0.755–2.020	0.401
ECOG PS	0 vs 1	0.675	0.401–1.134	0.137
Comorbidity	No vs yes	0.870	0.540–1.402	0.567
Tumor site	Gallbladder vs bile duct	0.914	0.543–1.538	0.735
TNM-stage	I–II vs III–IVA	1.149	0.565–2.334	0.701
T-stage	T1-T2 vs T3-T4	0.650	0.364–1.159	0.145
Lymph node	N- vs N+	0.477	0.285–0.799	0.005
Pathological differentiation	Poor vs well-moderately	1.167	0.698–1.952	0.556
	Unknown vs well-moderately	1.075	0.487–2.374	0.859
	Unknown vs poor	1.086	0.468–2.519	0.848
Chemotherapy regimen	GS vs GP/GEMOX	0.627	0.387–1.016	0.058
Chemotherapy cycles	<6 vs 6–8	1.828	1.117–2.993	0.016

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; GP, gemcitabine plus cisplatin; GEMOX, gemcitabine plus oxaliplatin; GS, gemcitabine plus S-1; N-, lymph node negative; N+, lymph node negative; RFS, relapse-free survival.

Figure 2 Kaplan–Meier Curves of RFS based on chemotherapy regime.

Abbreviations: GP, gemcitabine plus cisplatin; GEMOX, gemcitabine plus oxaliplatin; GS, gemcitabine plus S-1; RFS, relapse-free survival.

Figure 3 Kaplan–Meier Curves of RFS based on lymph node involvement (A) and chemotherapy cycles (B).

Abbreviations: N-, lymph node negative; N+, lymph node negative; RFS, relapse-free survival.

Figure 4 Landmark analysis based on chemotherapy cycles.

Figure 5 RFS benefits of different chemotherapy regimens in subgroups.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; GP, gemcitabine plus cisplatin; GEMOX, gemcitabine plus oxaliplatin; GS, gemcitabine plus S-1; N-, lymph node negative; N+, lymph node negative.

Table 4 Treatment-Related Adverse Events

Events (Grade 3–4)	Total (N/%)	GP/GEMOX (N/%)	GS (N/%)	P value
Hematologic toxic effects
Neutropenia	23 (17%)	19 (23%)	4(7%)	0.013
Thrombocytopenia	17(13%)	14 (17%)	5(9%)	0.176
Hypohemia	11(8%)	8 (10%)	3(5%)	0.353
Non-hematologic toxic effects
Fatigue	12(9%)	9 (11%)	3(5%)	0.240
Nausea	17(13%)	14 (17%)	3(5%)	0.041
Vomiting	17(13%)	15 (19%)	2(4%)	0.010
Impaired renal function	6(4%)	5 (6%)	1(2%)	0.199
Infection	2(1%)	2 (2%)	0(0%)	0.148
Increased ALT/AST	13(10%)	7 (9%)	6(11%)	0.659

Abbreviations: GP, gemcitabine plus cisplatin; GEMOX, gemcitabine plus oxaliplatin; GS, gemcitabine plus S-1; ALT, alanine aminotransferase; AST, aspartate aminotransferase.