title: Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer.
abstract: OBJECTIVE
  We wanted to evaluate the efficacy, defined as 2-year disease-free survival (DFS), and safety of bevacizumab/chemoradiation in preoperative and adjuvant settings for patients with stage II/III rectal cancer.
  
  
  METHODS
  Eligible patients had stage II/III rectal adenocarcinoma, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and adequate organ function, and received preoperative (cohort A) or adjuvant (cohort B) treatment at physician discretion. Patients received 5-fluorouracil (5-FU) as an intravenous infusion (IVCI) 225 mg/m(2)/d on days 1-42, bevacizumab 5 mg/kg intravenously (I.V.) on days 1 and 15 (cohort A), or every 2 weeks (cohort B), with radiation therapy to 50.4 Gy. After surgery (cohort A) or chemoradiation (cohort B), FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) and bevacizumab were administered for 4 months and then bevacizumab was given alone for up to 1 year.
  
  
  RESULTS
  Sixty-six patients (cohort A = 35; cohort B = 31) were enrolled from August 2006-April 2009: median age was 57 years; male patients, 62%; ECOG PS 0, 75%; stage II/III, 31%/69%. In cohort A, the complete pathologic response (pCR) rate was 29% (11% microscopic residual disease, 49% gross disease). Four patients did not undergo surgery (toxicity, 2 patients; progressive disease, 1 patient; patient decision, 1 patient). One- and 2-year DFS for cohorts A/B were 85%/not reached and 97%/89%, respectively (median survival not reached for either cohort). Frequent grade 3/4 toxicity included diarrhea (A cohort, 14%; B cohort, 29%), neutropenia (A cohort, 14%, B cohort, 23%), mucositis (A cohort, 23%, B cohort, 0%), and fatigue (A cohort, 6%, B cohort, 10%). Other serious toxicity included bowel perforation and pelvic infection (cohort A, 1 patient each), bowel perforation (2 patients), anal wound dehiscence (1 patient), perianal infection (2 patients), and rectovaginal fistula (1 patient) (cohort B), without treatment-related death in either cohort.
  
  
  CONCLUSIONS
  Bevacizumab can be added to standard preoperative and adjuvant chemoradiation in most patients with expected and manageable toxicity and may increase treatment efficacy.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Michael
authors.initials: M
authors.lastname: McCleod
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Shipley
authors.forename: Edward
authors.initials: E
authors.lastname: Arrowsmith
authors.forename: E Kirk
authors.initials: EK
authors.lastname: Barnes
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil