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

• Published in: Journal of cancer research and clinical oncology Vol. 139; no. 4; pp. 681 - 689
• Main Authors: Haas, Michael, Heinemann, Volker, Kullmann, Frank, Laubender, Rüdiger P., Klose, Christina, Bruns, Christiane J., Holdenrieder, Stefan, Modest, Dominik P., Schulz, Christoph, Boeck, Stefan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2013; Springer; Springer Nature B.V
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bilirubin; Bilirubin - metabolism; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - metabolism; C-Reactive Protein - metabolism; CA-19-9 Antigen - metabolism; Cancer Research; Carcinoembryonic Antigen - metabolism; Carcinoma, Acinar Cell - drug therapy; Carcinoma, Acinar Cell - metabolism; Carcinoma, Acinar Cell - mortality; Carcinoma, Acinar Cell - secondary; Chemotherapy; Clinical trials; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Hematology; Humans; Internal Medicine; L-Lactate Dehydrogenase - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Metastases; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Grading; Oncology; Original Paper; Palliation; Palliative Care; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Patients; Pharmacology. Drug treatments; Prognosis; Prospective Studies; Retrospective Studies; Survival Rate; Tumor markers; Tumors; Gemcitabine; Prognostic factor; Pancreatic cancer; Antineoplastic agent; Prognosis; Multicenter study; Bilirubin; Metastasis; Pancreas cancer; Advanced stage; Pyrimidine nucleoside; Pancreatic disease; Human; Patient; Malignant tumor; Chemotherapy; Treatment; Antimetabolic; Analysis; Pyrimidine derivatives; Digestive diseases; Locally advanced stage; Fluorine Organic compounds; Antigen CA 19 9; Cancer
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-012-1371-3

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.