title: Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial.
abstract: BACKGROUND
  Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer.
  
  
  METHODS
  For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m(2) orally twice a day on days 1-14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939.
  
  
  RESULTS
  From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3-11·4] vs 5·1 months [4·2-6·3]; hazard ratio 0·53 [0·41-0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]).
  
  
  CONCLUSIONS
  The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer.
  
  
  BACKGROUND
  F Hoffmann-La Roche.
authors.affiliation: Royal Marsden Hospital, London, UK. Electronic address: david.cunningham@rmh.nhs.uk.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Lang
authors.affiliation: Hospital de Sant Pau de Barcelona, Barcelona, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Marcuello
authors.affiliation: National Cancer Institute Giovanni Paolo II, Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.affiliation: Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Ocvirk
authors.affiliation: Division of Haematology and Oncology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea.
authors.forename: Dong Bok
authors.initials: DB
authors.lastname: Shin
authors.affiliation: Department of Medical Oncology, The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Jonker
authors.affiliation: F Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Stuart
authors.initials: S
authors.lastname: Osborne
authors.affiliation: F Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Niko
authors.initials: N
authors.lastname: Andre
authors.affiliation: F Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Waterkamp
authors.affiliation: Christie Hospital, Withington, Manchester, UK.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Saunders
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil