A Multicenter Phase II Study of Gemcitabine plus S-1 Chemotherapy for Advanced Biliary Tract Cancer.
Gemcitabine (GEM) plus cisplatin (CDDP) chemotherapy has been used worldwide as the standard first-line treatment for advanced biliary tract cancer (BTC). A phase II trial has also suggested promising activity of GEM plus S-1 chemotherapy against advanced BTC. The aim of this study was to evaluate the efficacy and safety of GEM plus S-1 chemotherapy in patients with advanced BTC.



The eligibility criteria were as follows: histologically-proven BTC, unresectable or recurrent disease, ECOG performance status (PS) 0-1 regardless of previous treatment. Gemcitabine was administered intravenously at the dose of 1,000 mg/m2over 30 min on days 1 and 8, and S-1 was administered orally at doses of 60/80/100 mg/day based on the BSA, from day 1 to day 14, every 3 weeks. The primary endpoint was the response rate according to RECIST, ver. 1.1, and the secondary endpoints were the frequency/severity of toxicities, progression-free survival (PFS) and overall survival (OS).



A total of 38 patients were enrolled between August 2008 and November 2011. There were 19 men and 19 women, with a median age of 66 years (range=44-81 years). Seven patients had a previous history of first-line or adjuvant chemotherapy after surgery. The PS was 0 and 1 in 30 and 7 patients, respectively. The treatment response was classified as partial response in 6 patients (15.8%) and as stable disease in 18 patients (47.4%). The median PFS and OS were 5.8 and 15.9 months, respectively. The toxicity was generally mild, and the most common grade 3/4 toxicities were leukopenia (31.6%), neutropenia (36.8%), nausea/vomiting (2.6%), and diarrhea (2.6%). There was one treatment-related death due to interstitial pneumonia.



Our study revealed that gemcitabine plus S-1 chemotherapy was well-tolerated and exhibited favorable antitumor activity in patients with advanced BTC.
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Shiho
S
Arima
Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
Kyoko
K
Shimizu
Department of Surgery, The Jikei University Daisan Hospital, Tokyo, Japan.
Tomoyoshi
T
Okamoto
Third Department of Internal Medicine, Kyorin University Faculty of Medicine, Tokyo, Japan.
Masao
M
Toki
Department of Surgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
Yutaka
Y
Suzuki
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Naohiro
N
Okano
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Daisuke
D
Naruge
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Kirio
K
Kawai
Takaaki
T
Kobayashi
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Akiyoshi
A
Kasuga
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Hiroshi
H
Kitamura
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Atuko
A
Takasu
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Fumio
F
Nagashima
Department of Surgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
Masanori
M
Sugiyama
Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan jfuruse@ks.kyorin-u.ac.jp.
Junji
J
Furuse
D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine
Biliary tract cancer; S-1; chemotherapy; gemcitabine; phase II study