title: Phase I study of adjuvant gemcitabine or S-1 in patients with biliary tract cancers undergoing major hepatectomy: KHBO1003 study.
abstract: BACKGROUND
  Standardized adjuvant therapy is not performed after major hepatectomy for biliary tract cancer (BTC) because of frequent adverse events, which may be caused by insufficient liver function. Therefore, the aim of this multicenter study (KHBO1003) was to determine the safety protocol for adjuvant chemotherapy after major hepatectomy.
  
  
  METHODS
  Within 12 weeks of R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC, the following adjuvant chemotherapy was performed for 6 months: 800-1,000 mg/m(2) gemcitabine on days 1, 8, and 15 and then every 3-4 weeks or 40-80 mg/m(2)/day S-1 on days 1-28 and every 3-6 weeks. Major dose-limited toxicity (DLT) was defined as grade 4 hematotoxicity, grade 3/4 febrile neutropenia, grade 3/4 non-hematotoxicity, skipped gemcitabine on days 8 and 15, or halting the course at or after 14 days. Dose-escalation and de-escalation decisions were based on the continual reassessment method. Every three patients were alternately assigned to each arm.
  
  
  RESULTS
  Thirty-three patients (14 intrahepatic bile duct, 1 gall bladder, 18 extrahepatic bile duct) were enrolled in this study from February 2011 to July 2012 (n = 18 gemcitabine, n = 15 S-1). At 10% of DLT, the recommended dose was 1,000 mg/m(2) gemcitabine biweekly and 80 mg/m(2)/day S-1 on days 1-28 and every 6 weeks. Major DLT and adverse drug reactions were neutropenia. No grade 3 or 4 non-hematological adverse events were noted.
  
  
  CONCLUSIONS
  We determined RDs for gemcitabine and S-1 adjuvant chemotherapy after major hepatectomy with a DLT that does not exceed 10%.
authors: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan, s-kobayashi@umin.ac.jp.
authors: Shogo
authors: S
authors: Kobayashi
authors: Hiroaki
authors: H
authors: Nagano
authors: Daisuke
authors: D
authors: Sakai
authors: Hidetoshi
authors: H
authors: Eguchi
authors: Etsuro
authors: E
authors: Hatano
authors: Masashi
authors: M
authors: Kanai
authors: Satoru
authors: S
authors: Seo
authors: Kojiro
authors: K
authors: Taura
authors: Yutaka
authors: Y
authors: Fujiwara
authors: Tetsuo
authors: T
authors: Ajiki
authors: Shigekazu
authors: S
authors: Takemura
authors: Shoji
authors: S
authors: Kubo
authors: Hiroaki
authors: H
authors: Yanagimoto
authors: Hideyoshi
authors: H
authors: Toyokawa
authors: Akihito
authors: A
authors: Tsuji
authors: Hiroaki
authors: H
authors: Terajima
authors: Satoshi
authors: S
authors: Morita
authors: Tatsuya
authors: T
authors: Ioka
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D001661:Biliary Tract Neoplasms / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006498:Hepatectomy / Q000379:methods*; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D011182:Postoperative Care / Q000379:methods; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; D003841:Deoxycytidine; D005641:Tegafur; C104201:gimeracil; D000093542:Gemcitabine