title: An Australian translational study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™) [ASCENT].
abstract: BACKGROUND
  The use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a well-established first-line and second-line treatment for patients with metastatic colorectal cancer (mCRC). However, there remains a need for reproducible, validated, inexpensive and accessible prognostic markers to aid treatment selection. The optimal treatment duration and the role of bevacizumab in certain patient subgroups, considered at particular risk of bevacizumab-mediated toxicity, also require further investigation. The aim of the ASCENT study [an Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™)] is to evaluate the relationship between the host inflammatory response as measured by neutrophil/lymphocyte ratio (NLR) and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment.
  
  
  METHODS
  This open-label, prospective, single arm, phase IV, Australian multi-centre study evaluates the relationship between the host inflammatory response as measured by NLR and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. 150 patients will be recruited from 16 centres around Australia. Patients will receive trial treatments in two phases: Phase A: XELOX or mFOLFOX6 plus bevacizumab administered from study start until first disease progression; and Phase B: FOLFIRI plus bevacizumab administered from first disease progression until second disease progression. The primary analysis will test the association between NLR and progression free survival using a proportional Hazards Model. Secondary analyses will investigate whether the relationship can be improved upon with other prognostic biomarkers, and further characterise the safety of bevacizumab following treatment initiation, and when continued after progression in combination with standard chemotherapy regimens (presented through summary statistics and Kaplan Meier curves).
  
  
  CONCLUSIONS
  Quantifying the relationship between NLR and PFS will inform decision making on the extent to which this simple metric may be applied clinically.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01588990.
authors.affiliation: Royal North Shore Hospital, St Leonards, NSW 2065, Australia. stephen.clarke@sydney.edu.au
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
authors.forename: Matt
authors.initials: M
authors.lastname: Burge
authors.forename: Cassandra
authors.initials: C
authors.lastname: Cordwell
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
authors.forename: William
authors.initials: W
authors.lastname: Reece
authors.forename: Niall
authors.initials: N
authors.lastname: Tebbutt
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000097:blood* / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007249:Inflammation / Q000097:blood; D002955:Leucovorin / Q000008:administration & dosage; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage; D015203:Reproducibility of Results
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D011743:Pyrimidines; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; C030986:pyrimidine; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin