title: Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy.
abstract: BACKGROUND
  Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab.
  
  
  METHODS
  A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg(-1) per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0.
  
  
  RESULTS
  Overall, 57 patients (56%) developed ≥grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20%; P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications.
  
  
  CONCLUSIONS
  Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, P.O. Box 180, HUS Helsinki 00029, Finland. pia.osterlund@hus.fi
authors.forename: P
authors.initials: P
authors.lastname: Österlund
authors.forename: L-M
authors.initials: LM
authors.lastname: Soveri
authors.forename: H
authors.initials: H
authors.lastname: Isoniemi
authors.forename: T
authors.initials: T
authors.lastname: Poussa
authors.forename: T
authors.initials: T
authors.lastname: Alanko
authors.forename: P
authors.initials: P
authors.lastname: Bono
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002277:Carcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab