title: Preoperative radiotherapy combined with S-1 for advanced lower rectal cancer: phase I trial.
abstract: OBJECTIVE
  S-1 based chemoradiation is the recommended treatment for rectal cancer; however, the optimal scheduling and dosing are not yet established. A Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and to determine the recommended dose (RD).
  
  
  METHODS
  Conformal RT was given using 4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy. Concurrently S-1 was given twice daily throughout RT. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12cm of the anal verge suitable for curative resection. Surgery was performed 6 weeks from completion of preoperative chemoradiotherapy. The dose escalating from S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2).
  
  
  RESULTS
  Nine patients were valid for safety. In all patients, S-1 was administered. There was no dose-limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were enrolled in the dose-escalation phase. At dose Level 2, two patients developed DLT and this was considered the MTD. Objective response according to RECIST were observed in 5 of 9 patients who had measurable disease (56%).
  
  
  CONCLUSIONS
  The RD of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT combined with S-1 was feasible and well tolerated.
authors.affiliation: Department of Surgery and Transplantation, Tokushima University Hospital, Tokushima, Japan. morimoto@clin.med.tokushima-u.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Morimoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurita
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishioka
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Miyatani
authors.forename: Hideya
authors.initials: H
authors.lastname: Kashihara
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikushima
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D059248:Chemoradiotherapy; D003967:Diarrhea / Q000139:chemically induced; D019583:Dose Fractionation, Radiation; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D057234:Preoperative Period; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012007:Rectum / Q000601:surgery; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid