title: Phase I trial of neoadjuvant preoperative chemotherapy with S-1, oxaliplatin, and bevacizumab plus radiation in patients with locally advanced rectal cancer.
abstract: BACKGROUND
  This phase I study was performed to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicities (DLTs) of oxaliplatin combined with preoperative chemoradiotherapy with S-1, oxaliplatin, and bevacizumab in locally advanced rectal cancer.
  
  
  METHODS
  Eligible patients had a newly diagnosed clinical stage T1-4 N0-3 M0 rectal adenocarcinoma within 12 cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2 Gy daily fractions, 5 days/week, total dose 40 Gy) with concurrent S-1 (80 mg/m(2)/day orally, days 1-5, 8-12, 15-19, and 22-26), bevacizumab (90 min continuous intravenous infusion at 5 mg/kg, days 1 and 15), and oxaliplatin (120 min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40 mg/m(2)/day) was gradually increased to determine the MTD and RD. Surgery was performed 6 weeks after completion of preoperative chemoradiotherapy.
  
  
  RESULTS
  11 patients were enrolled. The MTD of oxaliplatin was considered to be 60 mg/m(2), because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50 mg/m(2). Of the patients who received oxaliplatin at ≤ RD, 5 (83.3%) had a clinical response [four pathological responses and one pathological complete response (Grade 3)].
  
  
  CONCLUSIONS
  With this new regimen, the MTD of oxaliplatin was 60 mg/m(2), and the RD for phase II studies was 50 mg/m(2). This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study.
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan, hiko03363@festa.ocn.ne.jp.
authors: Hirohiko
authors: H
authors: Sato
authors: Mitsuo
authors: M
authors: Shimada
authors: Nobuhiro
authors: N
authors: Kurita
authors: Takashi
authors: T
authors: Iwata
authors: Kozo
authors: K
authors: Yoshikawa
authors: Jun
authors: J
authors: Higashigima
authors: Motoya
authors: M
authors: Chikakio
authors: Hideya
authors: H
authors: Kashihara
authors: Chie
authors: C
authors: Takasu
authors: Noriko
authors: N
authors: Matsumoto
authors: Shozo
authors: S
authors: Eto
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D059248:Chemoradiotherapy; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D020266:Radiotherapy, Conformal; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012007:Rectum / Q000601:surgery; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid