Skip to main content

Advertisement

SpringerLink
Log in

Prognostic relevance of CA 19-9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

The objective of this study was to define prognostic serum biomarkers that could serve as surrogate survival endpoints during second-line treatment for advanced pancreatic cancer. This retrospective single-center study included patients treated with second-line therapy for advanced exocrine pancreatic cancer. A pretreatment value and at least one serial measurement during the first two cycles of second-line chemotherapy for CA 19-9, CEA, CRP, and LDH had to be available in order to evaluate the prognostic role of kinetics on overall survival. A cutoff of a >20% increase from baseline during treatment was defined in order to form groups with suspected different outcomes. The effect of serial biomarker changes on survival was modeled by Cox proportional hazards regression in univariate and multivariate analyses. Overall, 70 patients treated with second-line therapy for advanced disease were included; 94% had distant metastases at treatment initiation. Median time to progression was 2.7 months and median survival 5.4 months. Univariate analysis found that an increase of >20% during treatment was significantly associated with a worse overall survival for CA 19-9 (HR 2.00, p = 0.018), CEA (HR 2.38, p = 0.004), and CRP (HR 3.06, p < 0.001). These associations remained significant within multivariate analysis for CEA (HR 2.86, p = 0.001) and CRP (HR 3.20, p = 0.001). Serum biomarker kinetics might serve as useful prognostic tools during second-line chemotherapy in advanced pancreatic cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.

    CAS  PubMed  Google Scholar 

  3. Heinemann V. Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. Semin Oncol. 2002;29:9–16.

    CAS  PubMed  Google Scholar 

  4. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.

    Article  CAS  PubMed  Google Scholar 

  5. Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27:5513–18.

    Article  CAS  PubMed  Google Scholar 

  6. Boeck S, Heinemann V. The role of second-line chemotherapy after gemcitabine failure in patients with advanced pancreatic cancer. Future Oncol. 2008;4:41–50.

    Article  CAS  PubMed  Google Scholar 

  7. Nakachi K, Furuse J, Ishii H, Suzuki E, Yoshino M. Prognostic factors in patients with gemcitabine-refractory pancreatic cancer. Jpn J Clin Oncol. 2007;37:114–20.

    Article  PubMed  Google Scholar 

  8. Pelzer U, Kubica K, Stieler J, et al. A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results from the CONKO 003 study. J Clin Oncol. 2008;26(Suppl):abstr.4508.

    Google Scholar 

  9. Koprowski H, Steplewski Z, Mitchell K, et al. Colorectal carcinoma antigens detected by hybridoma antibodies. Somat Cell Genet. 1979;5:957–71.

    Article  CAS  PubMed  Google Scholar 

  10. Lamerz R. Role of tumour markers, cytogenetics. Ann Oncol. 1999;10 suppl 4:145–9.

    Article  PubMed  Google Scholar 

  11. Berger AC, Garcia M, Hoffman JP, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol. 2008;26:5918–22.

    Article  PubMed  Google Scholar 

  12. Stemmler J, Stieber P, Szymala AM, et al. Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin? Onkologie. 2003;26:462–7.

    Article  CAS  PubMed  Google Scholar 

  13. Ko AH, Hwang J, Venook AP, et al. Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer. Br J Cancer. 2005;93:195–9.

    Article  CAS  PubMed  Google Scholar 

  14. Reni M, Cereda S, Balzano G, et al. Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma. Cancer. 2009;115:2630–9.

    Article  CAS  PubMed  Google Scholar 

  15. Hess V, Glimelius B, Grawe P, et al. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. Lancet Oncol. 2008;9:132–8.

    Article  CAS  PubMed  Google Scholar 

  16. Mann DV, Edwards R, Ho S, Lau WY, Glazer G. Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000;26:474–9.

    Article  CAS  PubMed  Google Scholar 

  17. Maréchal R, Demols A, Gay F, et al. Prognostic factors and prognostic index for chemonaïve and gemcitabine-refractory patients with advanced pancreatic cancer. Oncology. 2007;73:41–51.

    Article  PubMed  Google Scholar 

  18. Sawaki A, Kanemitsu Y, Mizuno N, et al. Practical prognostic index for patients with metastatic pancreatic cancer treated with gemcitabine. J Gastroenterol Hepatol. 2008;23:1292–7.

    Article  CAS  PubMed  Google Scholar 

  19. van Cutsem E, Vervenne WL, Bennouna J, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol. 2009;27:2231–7.

    Article  PubMed  Google Scholar 

  20. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  21. Brambs HJ, Claussen CD. Pancreatic and ampullary carcinoma. Ultrasound, computed tomography, magnetic resonance imaging and angiography. Endoscopy. 1993;25:58–68.

    Article  CAS  PubMed  Google Scholar 

  22. Reni M, Berardi R, Mambrini A, et al. A multi-centre retrospective review of second-line therapy in advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2008;62:673–8.

    Article  CAS  PubMed  Google Scholar 

  23. Tanaka T, Ikeda M, Okusaka T, et al. Prognostic factors in Japanese patients with advanced pancreatic cancer treated with single-agent gemcitabine as first-line therapy. Jpn J Clin Oncol. 2008;38:755–61.

    Article  PubMed  Google Scholar 

  24. Tas F, Aykan F, Alici S, et al. Prognostic factors in pancreatic carcinoma: serum LDH levels predict survival in metastatic disease. Am J Clin Oncol. 2001;24:547–50.

    Article  CAS  PubMed  Google Scholar 

  25. Kulke MH, Blaszkowsky LS, Ryan DP, et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007;25:4787–92.

    Article  CAS  PubMed  Google Scholar 

  26. Boeck S, Wilkowski R, Bruns CJ, et al. Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer. Oncology. 2007;73:221–7.

    Article  CAS  PubMed  Google Scholar 

  27. Firpo MA, Gay DZ, Granger SR, et al. Improved diagnosis of pancreatic adenocarcinoma using haptoglobin and serum amyloid A in a panel screen. World J Surg. 2009;33:716–22.

    Article  PubMed  Google Scholar 

  28. Buyse M, Piedbois P. On the relationship between response to treatment and survival time. Stat Med. 1996;15:2797–812.

    Article  CAS  PubMed  Google Scholar 

  29. Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1:710–19.

    CAS  PubMed  Google Scholar 

  30. Nakai Y, Kawabe T, Isayama H, et al. CA 19-9 response as an early indicator of the effectiveness of gemcitabine in patients with advanced pancreatic cancer. Oncology. 2008;75:120–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work is part of the doctoral thesis of Michael Haas.

Potential conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Internal Medicine III, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany

    Michael Haas, Volker Heinemann & Stefan Boeck

  2. Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany

    Rüdiger P. Laubender & Ulrich Mansmann

  3. Department of Clinical Chemistry, Klinikum Grosshadern, Ludwig-Maximilians University of Munich, Munich, Germany

    Petra Stieber & Stefan Holdenrieder

  4. Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany

    Christiane J. Bruns

  5. Department for Radiotherapy and Radiooncology, Klinik Bad Trissl, Oberaudorf, Germany

    Ralf Wilkowski

Authors
  1. Michael Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rüdiger P. Laubender
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Petra Stieber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefan Holdenrieder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christiane J. Bruns
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ralf Wilkowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ulrich Mansmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Volker Heinemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stefan Boeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan Boeck.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haas, M., Laubender, R.P., Stieber, P. et al. Prognostic relevance of CA 19-9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer. Tumor Biol. 31, 351–357 (2010). https://doi.org/10.1007/s13277-010-0044-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-010-0044-6

Keywords

Search

Navigation