title: Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy.
abstract: OBJECTIVE
  CA 19-9 is the only established tumor marker in pancreatic cancer (PC); the prognostic role of other serum markers like CEA, CRP, LDH or bilirubin has not yet been defined.
  
  
  METHODS
  We pooled pre-treatment data on CA 19-9, CEA, CRP, LDH and bilirubin levels from two German multicenter randomized phase II trials together with prospective patient data from one high-volume German Cancer Center. Marker levels were assessed locally before the start of palliative first-line therapy for advanced PC and serially during treatment (for CA 19-9 only). Clinical and biomarker data (overall 12 variables) were correlated with the efficacy endpoints time-to-progression (TTP) and overall survival (OS) by using uni- and multivariate Cox models.
  
  
  RESULTS
  Data from 291 patients were included in this pooled analysis; 253 patients (87 %) received treatment within prospective clinical trials. Median TTP in the study cohort was 5.1 months and median OS 9.0 months. In univariate analysis, pre-treatment CA 19-9 (HR 1.55), LDH (HR 2.04) and CEA (HR 1.89) levels were significantly associated with TTP. Regarding OS, baseline CA 19-9 (HR 1.46), LDH (HR 2.07), CRP (HR 1.69) and bilirubin (HR 1.62) were significant prognostic factors. Within multivariate analyses, pre-treatment log [CA 19-9] (as continuous variable for TTP) and log [bilirubin] as well as log [CRP] (for OS) had an independent prognostic value. A CA 19-9 decline of ≥25 % during the first two chemotherapy cycles was predictive for TTP and OS, independent of the applied CA 19-9 assay.
  
  
  CONCLUSIONS
  Baseline CA 19-9 and CA 19-9 kinetics during first-line chemotherapy are prognostic in advanced PC. Besides that finding other serum markers like CRP, LDH and bilirubin can also provide prognostic information on TTP and OS.
authors: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
authors: Michael
authors: M
authors: Haas
authors: Volker
authors: V
authors: Heinemann
authors: Frank
authors: F
authors: Kullmann
authors: Rüdiger P
authors: RP
authors: Laubender
authors: Christina
authors: C
authors: Klose
authors: Christiane J
authors: CJ
authors: Bruns
authors: Stefan
authors: S
authors: Holdenrieder
authors: Dominik P
authors: DP
authors: Modest
authors: Christoph
authors: C
authors: Schulz
authors: Stefan
authors: S
authors: Boeck
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001663:Bilirubin / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D018395:CA-19-9 Antigen / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D018267:Carcinoma, Acinar Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase; D001663:Bilirubin