title: Evaluation of hypertension and proteinuria as markers of efficacy in antiangiogenic therapy for metastatic colorectal cancer.
abstract: BACKGROUND
  The vascular endothelial growth factor pathway is strongly implicated in cancer-related angiogenesis. Antiangiogenic agents such as bevacizumab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome.
  
  
  METHODS
  We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with either bevacizumab or a tyrosine kinase inhibitor in combination with chemotherapy at The Christie Hospital from January 2006 to September 2009.
  
  
  RESULTS
  Of 90 patients evaluated, 50 were eligible. Seventeen (34%), 4 (8%), and 3 (6%) patients developed Common Toxicity Criteria (v 3.0) grades 1, 2, and 3 HTN, respectively. Response rates were 42% for patients with grades 0 to 1 HTN compared with 86% for patients with ≥grade 2 HTN (P=0.043). Median overall survival was 21.6 months for patients with grades 0 to 1 HTN and 25.2 months for patients with ≥grade 2 HTN (P=0.270). Twelve patients (24%) developed grade 1 PTN and 4 patients (8%) developed ≥grade 2 PTN. Median overall survival was 23.9 months for patients with grades 0 to 1 PTN and 4.2 months for those with ≥grade 2 PTN (P=0.028).
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to demonstrate the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for metastatic colorectal cancer. Although HTN is predictive of a significantly higher response rate, the development of PTN during treatment with bevacizumab or tyrosine kinase inhibitor portends poorer survival and should be evaluated prospectively.
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Khoja
authors.forename: Gireesh
authors.initials: G
authors.lastname: Kumaran
authors.forename: Ying Kiat
authors.initials: YK
authors.lastname: Zee
authors.forename: Nishanth
authors.initials: N
authors.lastname: Murukesh
authors.forename: Ric
authors.initials: R
authors.lastname: Swindell
authors.forename: Mark P
authors.initials: MP
authors.lastname: Saunders
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Clamp
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.forename: Greg
authors.initials: G
authors.lastname: Wilson
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Jayson
authors.forename: Jurjees
authors.initials: J
authors.lastname: Hasan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011507:Proteinuria / Q000139:chemically induced / Q000453:epidemiology; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab