title: Prognostic/predictive value of 207 serum factors in colorectal cancer treated with cediranib and/or chemotherapy.
abstract: BACKGROUND
  The prognostic and predictive value of multiple serum biomarkers was evaluated using samples from a randomised phase III study (HORIZON II) investigating chemotherapy with or without cediranib in metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Baseline levels of 207 protein markers were measured in serum samples from 582 HORIZON II (FOLFOX/XELOX plus cediranib 20 mg (n=330) or placebo (n=252)) patients. Median baseline values of each biomarker were used to categorise patients as high or low. Markers were then assessed for their association with efficacy, defined by progression-free survival (PFS) and overall survival (OS). A generalised boosted regression model identified markers of particular interest.
  
  
  RESULTS
  Correlation of protein levels with PFS and OS suggested that multiple factors had a prognostic value, independent of treatment arm, including IL-6, IL-8, C-reactive protein (CRP), ICAM-1 and carcinoembryonic antigen (CEA). Among the angiogenesis regulators, low levels of vascular endothelial growth factor (VEGF), VEGF-D, VEGFR-1, VEGFR-3, NRP1 and Tie-2 correlated with better outcome.
  
  
  CONCLUSIONS
  This large data set generated using serum samples from mCRC patients treated with chemotherapy and VEGF inhibitors, defines baseline characteristics for 207 serum proteins. Multiple prognostic factors were identified that could be disease related or predict which patients derive most benefit from 5-fluorouracil (5-FU)-based chemotherapy, meriting further exploration in prospective studies.
authors.affiliation: Clinical Oncology, AstaZeneca, Macclesfield, UK.
authors.forename: S K M
authors.initials: SK
authors.lastname: Spencer
authors.forename: A J C
authors.initials: AJ
authors.lastname: Pommier
authors.forename: S R
authors.initials: SR
authors.lastname: Morgan
authors.forename: S T
authors.initials: ST
authors.lastname: Barry
authors.forename: J D
authors.initials: JD
authors.lastname: Robertson
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
authors.forename: J M
authors.initials: JM
authors.lastname: Jürgensmeier
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010071:Oxaloacetates; D010919:Placebos; D011237:Predictive Value of Tests; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage*; D016019:Survival Analysis; D007211:Indoles
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D002955:Leucovorin; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D010919:Placebos; D011799:Quinazolines; C500926:cediranib; D007211:Indoles