title: Randomized phase II study of gemcitabine plus S-1 versus S-1 in advanced biliary tract cancer: a Japan Clinical Oncology Group trial (JCOG 0805).
abstract: The oral fluoropyrimidine, S-1, combined with or without gemcitabine is considered to be a promising agent for treating advanced biliary tract cancer; gemcitabine plus cisplatin is the current standard regimen. This randomized phase II trial was designed to evaluate the safety and efficacy of two regimens: gemcitabine plus S-1 (GS) (gemcitabine: 1000 mg/m(2) , day 1 and day 8; S-1: 60 mg/m(2) , twice daily on days 1-14, repeated every 3 weeks); and S-1 (80 mg/m(2) , days 1-28, given orally twice daily for 4 weeks, followed by a 2-week rest, repeated every 6 weeks). The regimen with a higher 1-year survival would be selected for a subsequent phase III trial. Between February 2009 and April 2010, 101 patients were randomized. For the GS (n = 51) and S-1 (n = 50) arms, the 1-year survival was 52.9% (95% confidence interval, 38.5-65.5) and 40.0% (95% confidence interval, 26.5-53.1), and the median survival times were 12.5 and 9.0 months, respectively. Grade 3/4 hematological toxicities were more frequent in the GS arm (leucocytes 29.4%, neutrophils 60.8%, hemoglobin 11.8%, platelets 11.8%) than in the S-1 arm (leucocytes 2.0%, neutrophils 4.0%, hemoglobin 4.0%, platelets 4.0%). Although two treatment-related deaths occurred in the GS arm, all other grade 3/4 non-hematological toxicities were reversible. In conclusion, GS was considered to be more promising and was selected as the test regimen for a subsequent phase III trial comparing GS with gemcitabine plus cisplatin combination therapy. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001685 (http://www.umin.ac.jp/ctr/index.htm).
authors.affiliation: Hepatobiliary and Pancreatic Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Ueno
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine