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

  • Michael Haas
  • Volker Heinemann
  • Frank Kullmann
  • Rüdiger P. Laubender
  • Christina Klose
  • Christiane J. Bruns
  • Stefan Holdenrieder
  • Dominik P. Modest
  • Christoph Schulz
  • Stefan Boeck
Original Paper

Abstract

Purpose

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.

Conclusion

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.

Keywords

Gemcitabine Pancreatic cancer Prognostic factor 

Notes

Acknowledgments

The authors would like to thank all patients and their families, nurses, study coordinators and investigators that actively participated in the Ro96 and the GEMOXCET study, thereby enabling this pooled analysis. This work is part of the doctoral thesis of Michael Haas.

Conflict of interest

All authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Michael Haas
    • 1
  • Volker Heinemann
    • 1
  • Frank Kullmann
    • 2
  • Rüdiger P. Laubender
    • 3
  • Christina Klose
    • 4
  • Christiane J. Bruns
    • 5
  • Stefan Holdenrieder
    • 6
  • Dominik P. Modest
    • 1
  • Christoph Schulz
    • 1
  • Stefan Boeck
    • 1
  1. 1.Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum GrosshadernLudwig-Maximilians-University of MunichMunichGermany
  2. 2.Department of Medicine I, Gastroenterology/OncologyKlinikum WeidenWeidenGermany
  3. 3.Institute of Medical Informatics, Biometry and EpidemiologyLudwig-Maximilians-University of MunichMunichGermany
  4. 4.Institute for Medical Biometry and InformaticsUniversity of HeidelbergHeidelbergGermany
  5. 5.Department of Surgery and Comprehensive Cancer Center, Klinikum GrosshadernLudwig-Maximilians-University of MunichMunichGermany
  6. 6.Institute of Clinical Chemistry and Clinical PharmacologyUniversity Hospital BonnBonnGermany

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