Watanabe A, Kida M, Miyazawa S, Iwai T, Okuwaki K, Kaneko T, Yamauchi H, Takezawa M, Imaizumi H, Koizumi W. Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer. World J Gastroenterol 2015; 21(19): 5979-5984 [PMID: 26019463 DOI: 10.3748/wjg.v21.i19.5979]
Corresponding Author of This Article
Mitsuhiro Kida MD, PhD, Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara City, Kanagawa 252-0374, Japan. m-kida@kitasato-u.ac.jp
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical Trials Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. May 21, 2015; 21(19): 5979-5984 Published online May 21, 2015. doi: 10.3748/wjg.v21.i19.5979
Table 1 Doses and treatment schedules for each level
Gemcitabine
Cisplatin
S-1 (mg/d, Days 1-7, 15-21)
(mg/m2, Days 1, 15)
BSA < 1.25
1.25 < BSA < 1.5
BSA > 1.5
Level -1
800
20
60
80
100
Level 0
800
25
60
80
100
Level 1
1000
25
60
80
100
Level 2
1000
25
80
100
120
Table 2 Patient characteristics
Characteristic
n (%)
Sex
Male
10 (83)
Female
2 (17)
Median age
69 (range 44-77)
Primary lesion
Intrahepatic
2 (17)
Extrahepatic
3 (25)
Gallbladder
7 (58)
Ampulla of vater
0 (0)
Disease status
Unresectable
12 (100)
Recurrent
0 (0)
Performance status (0/1)
12/0
Biliary drainage
6 (50)
Median CEA (ng/mL)
3 (range 1.1-33.4)
Median CA19-9 (U/mL)
156.5 (range 1.0- > 10000)
Table 3 Dose-limiting toxicities at each level
Level
Age
Sex
Primary lesion
Biliary drainage
DLT
Response (RECIST)
0
71
M
Extrahepatic
Yes
None
PR
0
73
M
Extrahepatic
Yes
None
SD
0
63
F
Gallbladder
No
None
PD
1
77
M
Intrahepatic
Yes
Gr 4 febrile neutropenia and leucopenia, Gr 3 thrombocytopenia
PD
1
67
M
Gallbladder
Yes
None
NE
1
64
M
Gallbladder
No
None
SD
1
70
M
Extrahepatic
Yes
None
SD
1
72
M
Gallbladder
No
None
PR
1
74
M
Gallbladder
No
None
PR
2
58
M
Intrahepatic
No
None
PR
2
68
F
Gallbladder
No
None
SD
2
44
M
Gallbladder
Yes
None
PD
Table 4 Hematologic adverse events during the first cycle
Level 0
(n = 3)
Level 1
(n = 6)
Level 2
(n = 3)
Gr 1-2
Gr 3-4
Gr 1-2
Gr 3-4
Gr 1-2
Gr 3-4
Neutropenia
0
0
0
1
0
1
Leucopenia
1
0
2
1
1
0
Thrombocytopenia
2
0
1
1
0
0
Anemia
2
0
1
0
0
0
Febrile neutropenia
NA
0
NA
1
NA
0
Table 5 Non-hematologic adverse events during the first cycle
Level 0
(n = 3)
Level 1
(n = 6)
Level 2
(n = 3)
Gr 1-2
Gr 3-4
Gr 1-2
Gr 3-4
Gr 1-2
Gr 3-4
Anorexia
2
0
1
0
2
0
Nausea
1
0
1
0
0
0
Vomiting
1
0
0
0
0
0
Fatigue
0
0
0
0
2
0
Constipation
1
0
1
0
0
0
Fever
1
0
2
0
0
0
Biliary tract infection
NA
3
NA
0
NA
1
Infections (others)
0
0
0
2
0
0
AST
3
0
2
0
0
0
ALT
2
0
2
0
0
0
Hyperbilirubinemia
2
0
1
0
1
0
Creatinine
0
0
3
0
0
0
Citation: Watanabe A, Kida M, Miyazawa S, Iwai T, Okuwaki K, Kaneko T, Yamauchi H, Takezawa M, Imaizumi H, Koizumi W. Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer. World J Gastroenterol 2015; 21(19): 5979-5984