title: A phase I trial of combination therapy using gemcitabine and S-1 concurrent with full-dose radiation for resectable pancreatic cancer.
abstract: OBJECTIVE
  Use of the fourth-generation oral fluoropyrimidine S-1 together with gemcitabine has shown striking anticancer effects. In this single-arm phase I trial of preoperative combination therapy using gemcitabine and S-1 concurrently with radiotherapy, we verified the safety and feasibility and determined the maximum-tolerated dose of each drug in patients with resectable pancreatic cancer.
  
  
  METHODS
  A standard 3+3 dose escalation scheme was used. Patients with cytologically or histologically proven resectable pancreatic ductal adenocarcinoma were administered 30-min intravenous gemcitabine infusions on days 1, 8, 22, and 29 and S-1 orally on days 1-5, 8-12, 22-26, and 29-33. A total radiation dose of 50.4 Gy (1.8 Gy/day, 5 times per week, 28 fractions) was concurrently delivered. Surgical exploration was scheduled 4-7 weeks after the final radiation fraction.
  
  
  RESULTS
  Twenty-one patients were enrolled. No treatment-related deaths occurred during this study. Recommended doses were determined to be 80 mg/m(2) of S-1 daily and 1,000 mg/m(2) of gemcitabine. CA19-9 was reduced to <50 % of baseline values in 12 (75 %) of 16 measurable patients. Nineteen of 21 enrolled patients successfully underwent surgical resection.
  
  
  CONCLUSIONS
  Preoperative chemoradiotherapy consisting of gemcitabine and S-1 concurrent with full-dose radiation is feasible and well tolerated.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita 565-0871, Osaka, Japan, heguchi@gesurg.med.osaka-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Naoki
authors.initials: N
authors.lastname: Hama
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Akita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kudo
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Isohashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D059248:Chemoradiotherapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine