title: Phase I trial of neoadjuvant chemoradiation with gemcitabine and surgical resection for cholangiocarcinoma patients (NACRAC study).
abstract: OBJECTIVE
  The feasibility of neoadjuvant chemoradiation therapy for cholangiocarcinoma, followed by conventional resection, has not been determined yet. Here, a phase I study of neoadjuvant chemoradiation therapy, named NACRAC, was performed to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of gemcitabine when combined with external beam radiation therapy for resectable cholangiocarcinoma.
  
  
  METHODS
  From August 2007 to June 2008, 12 patients provided informed consent. Preoperative radiation was administered in 1.8Gy daily fractions up to a total dose of 45Gy. Gemcitabine was administered at day 1 and 8 every three weeks. The initial dose of gemcitabine was started from 400mg/m2.
  
  
  RESULTS
  One patient was not able to start treatment because of bleeding caused by a duodenal ulcer and cholangitis. At 800mg/m2 of gemcitabine, one patient out of three failed to complete the treatment because of Grade 3 hematological toxicity. In another three cases of 800mg/m2, the second case could not complete the treatment because of cholangitis. Then, 600mg/m2 was determined to be the MTD, and the RD dose decided as 600mg/m2.
  
  
  CONCLUSIONS
  The RD of gemcitabine in NACRAC study was determined to be 600mg/m2. NACRAC study should proceed to a phase II trial to evaluate the effectiveness.
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Katayose
authors.forename: Toshiki
authors.initials: T
authors.lastname: Rikiyama
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Takanori
authors.initials: T
authors.lastname: Morikawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kanno
authors.forename: Morihisa
authors.initials: M
authors.lastname: Hirota
authors.forename: Kennichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Hisanori
authors.initials: H
authors.lastname: Ariga
authors.forename: Masaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Motoki
authors.initials: M
authors.lastname: Ohyauchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikeya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000473:pathology / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic; D059248:Chemoradiotherapy; D018281:Cholangiocarcinoma / Q000473:pathology / Q000628:therapy*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine