title: Evaluation of predictive markers for patients with advanced colorectal cancer.
abstract: BACKGROUND
  To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.
  
  
  METHODS
  One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses.
  
  
  RESULTS
  A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value.
  
  
  CONCLUSIONS
  Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. per.bystrom@akademiska.se
authors.forename: Per
authors.initials: P
authors.lastname: Byström
authors.forename: Åke
authors.initials: Å
authors.lastname: Berglund
authors.forename: Peter
authors.initials: P
authors.lastname: Nygren
authors.forename: Lisa
authors.initials: L
authors.lastname: Wernroth
authors.forename: Birgitta
authors.initials: B
authors.lastname: Johansson
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011228:Prealbumin / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D017457:Receptors, Albumin / Q000097:blood; D012680:Sensitivity and Specificity; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013548:Sweden; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019396:Tissue Polypeptide Antigen / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D011228:Prealbumin; D017457:Receptors, Albumin; D000685:Serum Amyloid A Protein; D019715:Tissue Inhibitor of Metalloproteinase-1; D019396:Tissue Polypeptide Antigen; C091986:transthyretin receptor; D000077146:Irinotecan; D002097:C-Reactive Protein; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin