A randomized phase II study of gemcitabine and S-1 combination therapy versus gemcitabine monotherapy for advanced biliary tract cancer.
OBJECTIVE
In order to confirm the impact of adding S-1 to gemcitabine, we conducted a randomized phase II study to compare the combination therapy of gemcitabine plus S-1 to gemcitabine monotherapy in patients with advanced biliary tract cancer.


METHODS
Sixty-two patients with advanced cholangiocarcinoma or gallbladder cancer were randomized to either the combination therapy of gemcitabine and S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 15 and S-1 40 mg/m(2) b.i.d. on days 1-14, repeated every 4 weeks) or gemcitabine monotherapy (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15, repeated every 4 weeks). The primary endpoint of this study was response rate, and the regimen which showed the better response rate was selected as a candidate of phase III study. Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria version 1.0.


RESULTS
The response rates of the combination therapy and the monotherapy were 20.0 and 9.4 %, respectively. The median time-to-progressions and overall survivals of these two treatments were nearly the same (5.6 vs. 4.3 months; 8.9 vs. 9.2 months). Adverse events occurred more frequently in the combination arm.


CONCLUSIONS
The combination therapy of gemcitabine and S-1 showed the better response rate, but the superiority of this combination therapy was not clear in total. Because the standard of care changed to the combination therapy with gemcitabine and cisplatin during this study, it is difficult to select this combination therapy with a 4-week regimen as a candidate of phase III study.
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Takashi
T
Sasaki
Hiroyuki
H
Isayama
Yousuke
Y
Nakai
Yukiko
Y
Ito
Ichiro
I
Yasuda
Nobuo
N
Toda
Hirofumi
H
Kogure
Keiji
K
Hanada
Hiroyuki
H
Maguchi
Naoki
N
Sasahira
Hideki
H
Kamada
Tsuyoshi
T
Mukai
Yoshihiro
Y
Okabe
Osamu
O
Hasebe
Iruru
I
Maetani
Kazuhiko
K
Koike
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010349:Patient Compliance; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine