title: Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: a phase II trial.
abstract: BACKGROUND
  To evaluate the safety and efficacy of pre-operative chemoradiation, using capecitabine, oxaliplatin and bevacizumab with standard doses of radiation, in patients with high-risk rectal cancer.
  
  
  METHODS
  Patients with locally advanced or low rectal cancer were treated with capecitabine 825 mg/m(2) twice daily on days 1-14 and 22-35, oxaliplatin 50mg/m(2) on days 1, 8, 22 and 29, bevacizumab 5mg/kg on days 14, 1, 15 and 29, and radiation 50.4 Gy in 28 fractions including boost. Total mesorectal excision was performed 7-9 weeks after chemoradiation. The primary end-point was complete tumour regression (ypT0NX) by central review.
  
  
  RESULTS
  Forty-two evaluable patients were enrolled, and 38 proceeded to definitive surgery. Eighteen patients (43%) had clinical T4 tumours and/or N2 tumours. Mean relative dose intensity was >90% for all systemic agents, and 97% for radiation. Grade 3/4 diarrhoea occurred in 10 patients (24%) and pain in 4 patients (10%) pre-operatively, while grade 3/4 pain, fatigue and infection were each reported among 5 patients (13%) post-operatively. Re-operation due to complications occurred in 4 patients (11%). Complete tumour regression (ypT0) was seen in 9 patients (23.7%) of which two had N1 disease and the pathological complete response (pCR) rate (ypT0N0) was 18.4%. Central review changed pathologic stage in six cases (16%).
  
  
  CONCLUSIONS
  In this study, pre-operative bevacizumab added to oxaliplatin, capecitabine and radiation was safe and resulted in a promising tumour regression rate. Surgical complications were closely monitored and occurred with the expected frequency. Central pathology review should be considered for trials with pathologic response as the primary end-point.
  
  
  BACKGROUND
  British Columbia Cancer Agency, Hoffmann-La Roche Canada and Sanofi-Aventis.
authors.affiliation: BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6. hkennecke@bccancer.bc.ca
authors.forename: Hagen
authors.initials: H
authors.lastname: Kennecke
authors.forename: Scott
authors.initials: S
authors.lastname: Berry
authors.forename: Ralph
authors.initials: R
authors.lastname: Wong
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.forename: Keith
authors.initials: K
authors.lastname: Tankel
authors.forename: Jacob
authors.initials: J
authors.lastname: Easaw
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rao
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Post
authors.forename: John
authors.initials: J
authors.lastname: Hay
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003107:Colorectal Surgery; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D057234:Preoperative Period; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil