Shinshu Med J, 65⑵：99～111, 2017

Adjuvant Chemotherapy with Gemcitabine for Resected Biliary
Tract Cancer : A Single-Arm Phase 2 Study
Noriyuki Kitagawa1）†, Hiroaki Motoyama1）†, Akira Kobayashi1）＊, Takahide Yokoyama1）
Akira Shimizu1）, Tsuyoshi Notake1）, Kentaro Fukushima1）, Hitoshi Masuo1）
Takahiro Yoshizawa1）, Teruomi Tsukahara2） and Shin-ichi Miyagawa1）
1） First Department of Surgery, Shinshu University School of Medicine
2） Department of Preventive Medicine and Public Health, Shinshu University School of Medicine

Objective : This phase 2, single-arm trial aimed to evaluate the efficacy and safety of gemcitabine in theadjuvant setting for patients with biliary tract carcinoma (BTC).
Method : Patients undergoing surgery subsequently received 6 cycles of adjuvant gemcitabine (1000 mg/m2)
intravenously over 30 minutes on days 1, 8, and 15 every 4 weeks. The primary end point was a two-year
disease-free survival (DFS) rate and secondary end points were a two-year overall survival (OS) rate, tolerability,
and the frequency of grade 3 or 4 toxicity.
Results : A total of 55 patients were enrolled. Primary tumor sites were intrahepatic bile duct in 14, extrahepatic
bile duct in 34, gallbladder in 3, and ampulla of Vater in 4. During median follow-up of 40 months, 34 patientsdeveloped disease recurrence. Two-year DFS and OS rates were 47.7 % and 78.2 %, and median DFS and OS
were 23 months and 46 months, respectively. The long-term outcomes in patients with extrahepatic bile duct
carcinoma were similar compared with a historical cohort who underwent surgery alone. The completion rate
and total dose intensity were 61.8 % and 70.3 %, respectively. Twenty-six patients (47.3 %) had grade 3 or 4
toxicity, none of which culminated in a fatal event.
Conclusion : The present study failed to show significant benefits of gemcitabine in the adjuvant setting forpatients with resected BTC, although the regimen was well tolerated. Shinshu Med J 65 : 99―111, 2017
(Received for publication September 8, 2016 ; accepted in revised form December 20, 2016)
Key words : biliary tract cancer, adjuvant chemotherapy, gemcitabine

7-53 % for gallbladder carcinoma (GBC)9）-11）, and 50-68 %Ⅰ Introduction

for carcinoma of the ampulla of Vater (CAV)12）-14）.

Complete surgical resection is the only modality

The main reason for this is the high rate of cancer

that offers a chance for long-term survival for bili­

recurrence, which occurs even after curative resec­

ary tract carcinoma (BTC). However, long-term out­tion15）-17）, and once the disease recurs, the prognosis

comes of patients treated with surgery alone remain

is extremely poor. To this end, adjuvant radiation

unsatisfactory, with a reported 5-year survival rate oftherapy or chemotherapy, or both, have been explored1）-3）

as a means of reducing the rate of disease re­4）-8）lapse16）18）-21）.

28-48 % for intrahepatic cholangiocarcinoma (ICC)24-50 % for extrahepatic bile duct carcinoma (EBC),,

So far, data supporting adjuvant chemotherapy for＊

Corresponding author : Akira Kobayashi

BTC are sparse. There was one phase III trial, eval­First Department of Surgery, Shinshu University School ofuating the efficacy of the adjuvant chemotherapy

Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
E-mail : kbys@shinshu-u.ac.jp†

Noriyuki Kitagawa and Hiroaki Motoyama contributed equallyto this work

No. 2, 2017using 5-FU and mitomycin C on long-term outcomesfor patients with pancreatobiliary malignancies.
This study showed that the adjuvant chemotherapy
99

Kitagawa・Motoyama・Kobayashi et al.

significantly prolonged the 5-year survival rate incycles of gemcitabine every 4 weeks, primarily with­patients with stage II or greater gallbladder cancer,

in 8 weeks following surgery. Each chemotherapy

whereas no significant difference was observed be­

cycle consisted of 3 weekly infusions of gemcitabine

tween patients with and without the adjuvant thera­

1,000 mg/m2 given by intravenous infusion during

py in pancreatic cancer, bile duct cancer, and CAV.

a 30-minute period, followed by a 1-week rest. No

Gemcitabine is a key drug of chemotherapy forpremedication was administered in each gemcitabine

pancreatic carcinoma. Previous study showed thattreatment. The treatment regimen was terminatedadministration of gemcitabine in an adjuvant settingin the case of disease progression, intolerable ad­significantly delayed the development of recurrent

verse events or patient refusal.

22）

disease compared with surgery alone . However,C

Toxicity and dose modification

there have been few published prospective studies

The toxicities were graded according to the Com­of adjuvant gemcitabine chemotherapy for resected

mon Terminology Criteria for Adverse Events ver­BTC. We therefore conducted a phase 2, single-arm

sion 3.023）. Gemcitabine doses should be interrupted

trial aimed at evaluating the efficacy and safety of

in cases of grade 2 or higher events and treatment

gemcitabine in the adjuvant setting for patients withshould be delayed until complete recovery or until

BTC.

the adverse event improves to grade 0 or 1. Gemcit­
abine was decreased by 20 % in subsequent cycles

Ⅱ MethodAat the first occurrence of a grade 4 toxicity, and it
was reduced by 40 % at the second occurrence of aPatient selection
Patients with histologically verified BTC were eli­

given grade 4 toxicity. Treatment with gemcitabine

gible if they had undergone macroscopically curative

was permanently stopped if, despite dose reduction,

resection and no prior chemotherapy and/or radio­a grade 4 toxicity occurred for the third time.

therapy. Additional eligibility requirements includ­D

Study end points

ed : 20 years ≤ age < 80 years ; Eastern Cooperative

The primary end point was a two-year disease-

Oncology Group performance status of 0-2 ; adequate

free survival (DFS) rate and secondary end points

3

were a two-year overall survival (OS) rate, tolerability,

neutrophil count ≥ 2,000/mm , hemoglobin ≥ 10 g/dl,

and the frequency of grade 3 or 4 toxicity. Tolerability

bone marrow function (leucocyte count ≥ 4,000/mm ,33

and platelet count ≥ 100,000/mm ), adequate liver

was further analyzed after the stratification of thefunction (serum albumin ≥ 3.0 g/dl, total bilirubin ≤patients according to whether they had undergone a

2 times the upper limit of normal (ULN) and aspar­

major hepatectomy, defined as the resection of threetate aminotransferase (AST)/alanine aminotransfer­or more Couinaud’s segments24）.

ase (ALT) ≤ 3 times ULN) ; adequate renal function

E

Statistical analyses(creatinine ≤ 1.0 mg/dL) ; and life expectancy ≥ 3

The trial was designed to have 80 % power to de­months. All patients provided written informed con­tect an increase in two-year DFS rate from 40 % in

sent. Exclusion criteria included contracting active

the historical cohort with surgery alone at our insti­

infection, synchronous cancer, pregnancy or lacta­tution to 60 % in patients receiving adjuvant gemcit­

tion, a history of severe drug allergy and other se­abine chemotherapy. A total of 48 patients would bevere comorbid diseases. The protocol was approved

required with a two-sided significance level of 5 %.

by the institutional review board at Shinshu Univer­To allow for dropouts and to ensure that we hadsity. All procedures were performed in accordance

sufficient evidence to meet the trial objectives, wewith the 1964 Declaration of Helsinki. Clinical trials

aimed to recruit 55 patients. All analyses were per­identification number was UMIN000014018.

formed on an intention-to-treat basis. Data were ex­Bpressed as medians with range. The significance of

Adjuvant chemotherapy with gemcitabine
Patients received adjuvant chemotherapy with 6100

differences between the groups was assessed by theShinshu Med J

Vol. 65

Adjuvant chemotherapy with gemcitabine for BTC

chi-square test, Fischerʼs exact test, unpaired Stu­(23.6 %), neutropenia (45.5 %), thrombocytopenia (1.8

dent’s t-test, Welch’s t-test, Mann-Whitney U test,%), and fatigue (1.8 %). There were no treatment-re­log-rank test and Cox’s proportional hazard model

lated deaths.

as appropriate. A p value less than .05 was used toDLong-term outcomesindicate a significant difference. All statistical analy­

During a median follow-up period of 40 months, ases were made using the JMP software version 10.0

total of 34 patients (61.8 %) developed tumor recur­(SAS Institute, Cary, North Carolina, USA).

rence with median time to recurrence of 11.5 months

Ⅲ
A

Results

Patient characteristics
Between April 2006 and February 2010, a total of

55 patients were enrolled in the present study with(range, 1.8-55.8 months). Liver was the most common
recurrence site (47.0 %) (Table 1). The 2-year DFS
rate and OS rate was 47.7 % and 78.2 % (Fig. 1A, B),
and median DFS and OS were 23 months and 46
months, respectively.

the diagnosis of intrahepatic cholangiocarcinoma

We analyzed the effectiveness of adjuvant chemo­(ICC) in 14, extrahepatic bile duct carcinoma (EBC)

therapy for patients with EBC in comparison within 34, gallbladder carcinoma (GBC) in 3, and carcino­

the historical cohort of surgery alone (n＝187), be­ma of the ampulla of Vater (CAV) in 4. The back­cause of the relatively smaller number of patientsground characteristics are summarized in Table 1.

with ICC, GBC and CAV. No significant difference

The median age was 67 (34-78) years. A median pre­was observed in clinicopathological data between pa­

operative CEA and CA19-9 values were 2.4 ng/mL

tients with and without adjuvant chemotherapy ex­

and 44.3 U/ml, respectively. The most frequently

cept for preoperative carcinoembryonic antigen

performed surgical procedure was hepatectomy with

(CEA) (Table 4). There was no statistically significant

bile duct resection (26 patients ; 47.3 %), followed bydifference in DFS (two-year DFS rate of 42.5 % vs.

pancreaticoduodenectomy (15 patients ; 27.2 %). In

49.8 %, p＝0.495) and OS (two-year OS rate of 76.5 %pathologic staging based on 7th edition Americanvs. 64.4 %, p＝0.568) between patients with and with­

Joint Committee on Cancer (AJCC) classification, al­out adjuvant chemotherapy (Fig. 2A, B). No signifi­

most three fourths were categorized as having T2 (ncant survival advantage was observed in EBC pa­＝21, 38.2 %) or T3 (n＝17, 30.9 %) primary tumors.

tients receiving adjuvant chemotherapy when the

Lymph node involvement was observed in 24 pa­

patients were stratified according to the presence ortients (43.6 %). An R0 resection was achieved in 41

absence of lymph node involvement or curability

patients (74.5 %).

(Fig. 3A-D).

B

Treatment administration
Thirty-four patients (61.8 %) received the full 6

ⅣDiscussion

cycles of adjuvant chemotherapy. The reasons forThis study tested the null hypothesis that adju­

withdrawal from treatment included tumor recur­vant gemcitabine chemotherapy increases two-year

rence (8 patients ; 38.1 %), adverse events (8 patients ;DFS rate from 40 % to 60 %. However, we failed to38.1 %), and patient preference (5 patients ; 23.8 %).

show a significant survival benefit of adjuvant che­

The median relative dose intensity (RDI) was 70.3 %motherapy. In a subgroup analysis, no significant dif­(range, 9.9-100 %). The completion rate and the RDI

ference was observed in DFS and OS between EBC

tended to be lower among patients who had under­

patients with and without adjuvant chemotherapy.

gone a major hepatectomy, compared with those who

Although a recent meta-analysis showed a survival

had not (p＝0.199 and 0.103, respectively) (Table 2).

benefit of adjuvant therapy for patients with lymphCnode involvement or those undergoing R1 resec­

Adverse events
The incidence of adverse events is shown in Table

tion25）, adjuvant chemotherapy did not prolong the

3. The grade 3 or 4 toxicities included leucopenia

survival of such high-risk patients in the present

No. 2, 2017101

Kitagawa・Motoyama・Kobayashi et al.
Table 1

Background characteristics and perioperative data of the patients who
received adjuvant chemotherapy (n＝55)a

Characteristic
Age (years)b
GenderMale
FemaleTumor location
Intrahepatic cholangiocarcinoma
Extrahepatic bile duct carcinoma
Gallbladder carcinoma
Carcinoma of the ampulla of Vater
CEA (ng/mL)b
CA19-9 (U/mL)b
Operative procedure
Hepatectomy with bile duct resection
Hepatectomy with PD
Hepatectomy
PD
Bile duct resection
AJCC grading
T
T1
T2
T3
T4
N
N0
N1
Stage
Stage Ⅰ
Stage Ⅱ
Stage Ⅲ
Stage Ⅳ
G
G1
G2
G3
G4
R
R0
R1
Postoperative course
Recurrence
Time-to-recurrence (months)b
Disease recurrence sites
Liver
Lymph nodeLocoregional
Other sites
Last follow-up
Alive
Dead
Cause of death
From disease
From other causes

67 (34-78)
36 (65.5)
19 (34.5)
14 (25.4)
34 (61.8)
3 (5.5)4 (7.3)2.4 (0.9-16.8)
44.3 (0.6-14155.0)
26 (47.3)
3 (5.5)8 (14.5)
15 (27.2)
3 (5.5)8 (14.5)
21 (38.2)
17 (30.9)9 (16.4)
31 (56.4)
24 (43.6)
12 (21.8)
23 (41.8)
11 (20.0)
9 (16.4)
35 (63.6)
8 (14.6)
11 (20.0)
1 (1.8)41 (74.5)
14 (25.5)
34 (61.8)
11.5 (1.8-55.8)
16 (47.0)
7 (20.6)
4 (11.8)
7 (20.6)
22 (40.0)33 (60.0)31 (93.9)
2 (6.1)a

Values in parentheses are percentages unless indicated otherwise.
Values in parentheses are ranges.
CEA, carcinoembryonic antigen ; CA19-9, carbohydrate antigen 19-9 ; PD,pancreaticoduodenectomy ; AJCC, American Joint Committee on Cancer.
b102

Shinshu Med J

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Adjuvant chemotherapy with gemcitabine for BTC
Table 2

Tolerability of adjuvant chemotherapy stratified according to whether a major
hepatectomy had been performeda
Major hepatectomyb

Completion rate (%)
Relative dose intensity (%)
a(n＝28)

Other operative procedures(n＝27)

P value

57.1
65.2 (9.9-100.0)

77.8
92.1 (10.7-100.0)

0.103
0.054

Values in parentheses are ranges.

b

Major hepatectomy was defined as removal of three or more Couinaud segments24.

Table 3

Adverse events as evaluated according to the Common
Terminology Criteria for Adverse Events (version 3.0)

Adverse event
Hematological
Leucopenia
Neutropenia
AnemiaThrombocytopenia
Non-hematological
Liver dysfunction
Fatigue
Anorexia
NauseaRash

Any grade (%)

Grade 3 or 4 (%)

43 (78.2)
42 (76.4)
24 (43.6)
25 (45.5)

13 (23.6)
25 (45.5)
0 (0.0)1 (1.8)6 (10.9)5 (9.1)
13 (23.6)
7 (12.7)
6 (10.9)

0 (0.0)1 (1.8)0 (0.0)0 (0.0)0 (0.0)study. Previous studies on postoperative adjuvantof these toxicities were transient, and no fatal event

15）
16）

occurred. Furthermore, the occurrence rate was compa­

18）
-20）
26）
-36）

. Although some studies have suggested

rable to that of the previously reported phase 3 trial of

hopeful effects of adjuvant treatment, others could not

adjuvant gemcitabine for resected pancreatic carci­

reveal that adjuvant treatments contribute to delaying

noma in Japan, JSAP-02 (70.0 %)38）.

treatment of BTC are summarized in Table 5

the development of recurrence and prolonged survival.

Considering that gemcitabine is rapidly deaminat­

In particular, 2 RCTs failed to demonstrate signifi­

ed to its inactive metabolite, 2, 2-difluorodeoxyuri­

cant benefit for adjuvant chemotherapy in patients

dine, by cytidine deaminase, which abounds in the

15）
36）

. Thus, at present,

liver39）40）, the removal of a large amount of liver pa­

the evidences seems to be insufficient support thisrenchyma might enhance the toxicity of gemcit­

treatment strategy, in spite of its worldwide adop­abine, making the continuation of chemotherapy dif­with curatively resected BTC

37）tion in many major institutions .

ficult. Indeed, two recent phase I studies examining

Previous study demonstrated that the incidence ofadjuvant gemcitabine monotherapy in patients withserious adverse events was significantly lower in pa­

BTC undergoing a major hepatectomy revealed thattients treated with adjuvant gemcitabine alone than

the recommended dose of gemcitabine was muchthat in patients treated with fluorouracil plus leucov­

lower than the regular dose for unresectable and re­orin (30 % vs. 49 %, p < 0.01) for resected periampul­

current BTC21）41）. In line with these findings, thelary carcinoma36）. In the present study, adjuvant gem­

present study showed that the completion rate andcitabine could be safely administered to patients with

the RDI tended to be lower among patients who had

resected BTC. Although 47.3 % of patients experienced

undergone a major hepatectomy, compared withgrade 3 or 4 neutropenia during the treatment, mostthose who had not.

No. 2, 2017103

Kitagawa・Motoyama・Kobayashi et al.

Ａ

No. at risk

55

48

38

32

26

Ｂ

Fig. 1 The disease-free survival (DFS) (A)and overall survival (OS) (B) curves forpatients receiving adjuvant chemothera­py using gemcitabine. The 2-year DFS
and OS rates were 47.7 % and 78.2 %,respectively.

No. at risk

55

55

51

48

44

Table 4 Clinicopathological data of patients with extrahepatic biliary carcinoma stratified
according to whether adjuvant chemotherapy was performeda
Characteristic
Age (years)
Gender (male/female)
AJCC grading
T (T1/T2/T3/T4)
N (N0/N1)
Stage (I/II/III/IV)
G (G1/G2/G3/G4)
R (R0/R1)

Adjuvant chemotherapy(n＝34)

Surgery alone(n＝187)

P value

67 (34-78)
29/5

69 (39-84)
135/52

0.302
0.108

5/16/12/1
20/14
9/15/9/1
20/7/7/0
26/8

29/91/49/18
106/8143/76/50/18
103/57/26/1
161/26

0.497
0.817
0.631
0.555
0.152

a

Values in parentheses are ranges.
AJCC, American Joint Committee on Cancer.

An analysis of initial recurrence site in the pres­Our results are in line with the previous studies ofent study showed that distant metastasis occurred

hilar cholangiocarcionoma42）, distal cholangiocarcino­more frequently than local recurrence, and the mostma32）43）, and carcinoma of the ampulla of Vater14）44）45）.

prevalent site of distant metastasis was the liver.

Considering these results, although it remains con­

104

Shinshu Med J

Vol. 65

Adjuvant chemotherapy with gemcitabine for BTC

Ａ

p = 0.495

No. at risk
Adjuvant chemotherapy
Surgery alone

34
187

29
163

23
129

19
103

15
91

Ｂ

p = 0.373

u ger
No. atrisk
Adjuvant chemotherapy
Surgery alone

34
187

34
180

31
161

29
136

27
118

Adjuvant chemotherapy
Surgery alonejFig. 2 Comparison of DFS and OS between extrahepatic bile duct carcinoma patients with and without
adjuvant chemotherapy. There was no statistically significant difference in 2-year DFS and OS rates
between two groups (42.5 % vs. 49.8 %, p＝0.495, and 76.5 % vs. 64.4 %, p＝0.568, respectively).

troversial whether systemic chemotherapy or radio­

gemcitabine-based combined therapy49）50） because oftherapy is suitable for adjuvant treatment for resect­its superior anti-tumor effect51）. In the adjuvant set­ed BTC, systemic therapy could play a role as anting, there was no previous study in the English lit­

adjuvant treatment modality. Indeed, a meta-analy­

erature except for a report from Murakami et al.

sis demonstrated that patients receiving chemother­

They retrospectively studied the effect of gemcit­

apy or chemoradiotherapy showed better long-term

abine plus S-1 chemotherapy for resected BTC, and25）

outcomes than those undergoing radiotherapy alone .

showed that the combined regimen contributed to

Although gemcitabine monotherapy was used for

improved long-term outcomes in patients with In­

advanced BTC as the community standard in the

ternational Union Against Cancer stage II BTC19）.

2000s46）-48）, the first-line chemotherapeutic regimen

Further studies are needed to develop the effective regi­

for advanced BTC is, at present, considered to be

men of adjuvant chemotherapy for resected BTC.

No. 2, 2017

105

106

Shinshu Med J

23
144

18
99

18
115

R0 (n = 187)

1782

N0 (n = 126)

15
92

11
82

10
68

No. at risk
Adjuvant chemotherapy
Surgery aloneＤ

No. at risk
Adjuvant chemotherapy
Surgery alone

Adjuvant chemotherapy
Surgery alone

p = 0.585

1473

p = 0.167

Ｂ

8
26

14
81

7
20

12
65

6
15

R1 (n = 34)

747

N1 (n = 95)

Fig. 3 Effects of adjuvant chemotherapy in patients with extrahepatic bile duct carcinoma stratified according to their N or R
categories. No significant prolongation of the DFS was observed among patients receiving adjuvant chemotherapy in all
the subgroups. A) N0 (n＝126) ; B) N1 (n＝95) ; C) R0 (n＝187) ; D) R1 (n＝34).

No. at risk
Adjuvant chemotherapy 26
Surgery alone
161

Ｃ

No. at risk
Adjuvant chemotherapy 20
Surgery alone
106

Ａ

5
12

p = 0.964631

p = 0.679

5
10

6
24

Kitagawa・Motoyama・Kobayashi et al.

Vol. 65

Adjuvant chemotherapy with gemcitabine for BTC
Table 5 Literature review of long-term outcomes of patients with resected biliary tract cancer who received
adjuvant therapy (published after 2000)
Adjuvant therapy

5-year DFS rate (%)

5-year OS rate (%)

Adjuvant Surgery
therapy alone

CT

RT

Adjuvant Surgery
P valuetherapy alone

Adjuvant Surgery
P valuetherapy alone

2000 EBC

28

19

NA

ERBT

NR

NA

NA

34

13

0.014

2002 GBC

21

NA

5FU

ERBT

NR

NR

NR

33

NA

NA

Kim18）a

2002 EBC

84

NA

5FU

ERBT

26

NA

NA

31

NA

NA

Nakeeb28）a

2002 ICC, EBC,

42

NA

5FU or GEM ERBT

NR

NA

NA

13

NA

NA

2002 EBC

58

60

5FU＋MMC NA

21

15

0.889

27

24

NS

GBC

69

43

5FU＋MMC NA

20

12

0.021

26

14

0.037

AuthorYear

Todoroki26）a
Kresl27）aTumor
location

No. of patients

GBC
Takada15）b

CAV

24

24

5FU＋MMC NA

25

21

0.900

28

34

NS

Gerhards29）a

2003 EBC

71

20

NA

ERBT±ILRT

NR

NA

NA

NR

NR

< 0.050

Sikora30）a2005 CAV

49

55

5FU

ERBT

NR

NR

NR

28

38

0.330

Czito16）a2005 GBC

22

NA

NA

ERBT

33

NA

NA

37

NA

NA

Sagawa31）a2005 EBC

39

30

NA

ERBT±ILRT

NR

NR

NR

24

NR

0.554

Hughes32）a

2007 EBC

34

30

5FU

ERBT

NR

NR

NR

35

27

< 0.040

Krishnan33）a

2008 CAV

55

41

5FU or Cap

ERBT

NR

NR

NR

60

69

0.530

Borghero34）a

2008 EBC

42

23

5FU or Cap

ERBT

NR

NR

NR

36

42

0.590

Nelson20）a

2009 EBC

45

NA

5FU

ERBT

37

NA

NA

33

NA

NA

Gold35）a2009 GBC

25

48

5FU

ERBT

NR

NA

NA

NR

NR

0.560

50

53

GEM＋S－1

NA

60

NR

NR

57

24

< 0.001(AJCC stage
Ⅰ or Ⅱ )Murakami19）c

2009 EBC, GBC,CAV(UICC stage
Ⅱ)

Neoptolemos36）b 2012 EBC, CAV
Present Studyc

2015 ICC, EBC,

141

144

GEM

NA

NR

NR

NR

NR

NR

0.230

143

144

5FU＋FA

NA

NR

NR

NR

NR

NR

0.740

55

NA

GEM

NA

33

NA

NA

37

NA

NA

GBC, CAVa

A retrospective study
A prospective randomized controlled trialc
A prospective study compared to historical control
DFS, disease-free survival ; OS, overall survival ; CT, chemotherapy ; RT, radiation therapy ; EBC, extrahepatic bile duct
carcinoma ; NA, not applicable ; ERBT, external-beam radiation therapy ; NR, details not reported ; GBC, gallbladder carci­
noma ; ICC, intrahepatic cholangiocarcinoma ; 5FU, 5-fluorouracil ; GEM, gemcitabine ; MMC, mitomicin C ; NS, not signifi­
cant ; CAV, carcinoma of the ampulla of Vater ; ILRT, intraluminal radiation therapy ; Cap, capecitabine ; AJCC, American
Joint Committee on Cancer ; UICC, International Union Against Cancer ; FA, folinic acid.
b

There were several limitations in this study. The

each tumor type of BTC. Despite these limitations,study design was single-arm. The most important

however, we believe that our results are of interest,

limitation of the present study was the heterogene­because there have been so few reports in the En­

ity of the study population, consisting of all types ofglish literature of a phase 2 trial of adjuvant gemcit­

BTC including ICC, EBC, GBC, and CAV. Some re­abine monotherapy for resected BTC.

searchers have reported that the biological behavior

In conclusion, the present study failed to show sig­might be different among the tumor types based onnificant benefits of gemcitabine in the adjuvant set­

the results of sensitivity to non-surgical treatmentsting for patients with resected BTC, although the

36）
52）
-54）

. There­regimen was well tolerated. Further investigation offore, a stratified analysis according to tumor typeadjuvant treatments might be needed to improve long-

may reveal the true impact of adjuvant treatment interm outcomes in BTC patients.

36）
55）
56）

or survival profile after surgery

No. 2, 2017107

Kitagawa・Motoyama・Kobayashi et al.

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