title: Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study.
abstract: BACKGROUND
  In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes.
  
  
  METHODS
  This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate.
  
  
  RESULTS
  Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B).
  
  
  CONCLUSIONS
  Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.
authors.affiliation: Department of Medical Oncology, University Hospital of Besançon and CIC-BT506, Besançon. Electronic address: christophe.borg@efs.sante.fr.
authors.forename: C
authors.initials: C
authors.lastname: Borg
authors.affiliation: Department of Medical Oncology, Saint Antoine Hospital and Pierre and Marie Curie University, Paris.
authors.forename: T
authors.initials: T
authors.lastname: André
authors.affiliation: Department of Digestive and Liver Surgery, University Hospital of Besançon, Besançon.
authors.forename: G
authors.initials: G
authors.lastname: Mantion
authors.affiliation: Department of Radiology, Tenon Hospital, Paris.
authors.forename: F
authors.initials: F
authors.lastname: Boudghène
authors.affiliation: Department of Radiotherapy, Lyon-Sud Hospital Center, Lyon.
authors.forename: F
authors.initials: F
authors.lastname: Mornex
authors.affiliation: Department of Radiotherapy, Georges-François-Leclerc Center, Dijon.
authors.forename: P
authors.initials: P
authors.lastname: Maingon
authors.affiliation: Department of Medical Oncology, Oscar Lambret Center, Lille.
authors.forename: A
authors.initials: A
authors.lastname: Adenis
authors.affiliation: Department of Radiotherapy, Centre de Lutte Contre le Cancer Val D'Aurelle, Montpellier.
authors.forename: D
authors.initials: D
authors.lastname: Azria
authors.affiliation: Roche Laboratories, Boulogne-Billancourt.
authors.forename: M
authors.initials: M
authors.lastname: Piutti
authors.affiliation: Roche Laboratories, Boulogne-Billancourt.
authors.forename: O
authors.initials: O
authors.lastname: Morsli
authors.affiliation: Department of Radiotherapy, University Hospital of Besançon, Besançon, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Bosset
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D003841:Deoxycytidine / Q000008:administration & dosage; D013505:Digestive System Surgical Procedures; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil
keywords: 5-FU; bevacizumab; chemoradiotherapy; neoadjuvant; oxaliplatin; rectal cancer