Cytokeratin 19-fragments (CYFRA 21-1) as a novel serum biomarker for response and survival in patients with advanced pancreatic cancer

• Published in: British journal of cancer 2013-04, Vol.108 (8), p.1684-1694
• Main Authors: Boeck, S, Wittwer, C, Heinemann, V, Haas, M, Kern, C, Stieber, P, Nagel, D, Holdenrieder, S
• Format: Article
• Language: English
• Subjects: 692/699/67/1504/1713; 692/699/67/1857; 692/700/1750; 692/700/565/1436/99; Adult; Aged; Albumins - therapeutic use; Antigens, Neoplasm - blood; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Axitinib; Biological and medical sciences; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; CA-19-9 Antigen - blood; Cancer Research; Capecitabine; Carcinoembryonic Antigen - blood; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Drug Resistance; Epidemiology; Erlotinib Hydrochloride; Everolimus; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Imidazoles - administration & dosage; Indazoles - administration & dosage; Keratin-19 - blood; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multivariate Analysis; Oncology; Paclitaxel - therapeutic use; Palliative Care; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - drug therapy; Piperazines - administration & dosage; Prospective Studies; Quinazolines - administration & dosage; Sirolimus - administration & dosage; Sirolimus - analogs & derivatives; Sulfonamides - administration & dosage; Survival Rate; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.158

Background: CYFRA 21-1 serves as biomarker in several epithelial malignancies. However, its role in pancreatic cancer (PC) has not yet been investigated. Methods: Within a prospective single-centre study serial blood samples were collected from patients with confirmed advanced PC. Pre-treatment values and weekly measurements of CYFRA 21-1, carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (assessed by Elecsys 2010, Roche Diagnostics) during palliative first-line chemotherapy were obtained. Biomarker data were correlated with objective response (determined by RECIST) as well as time to progression (TTP) and overall survival (OS) using uni- and multivariate analyses. Results: Seventy-eight patients were included, 45% of these received treatment in prospective clinical trials. Median TTP was 3.9 months, median OS 7.7 months. Pre-treatment CYFRA 21-1 levels were significantly associated with performance status ( P =0.0399) and stage of disease ( P =0.0001). Marker values before chemotherapy and at the 2-month staging of all three markers were considered significant predictors for objective treatment response. Pre-treatment CYFRA 21-1 levels, as well as CA 19-9 values, could be applied to define subgroups (categorised by tertiles) with a different OS outcome (CYFRA: 14.8 vs 7.1 vs 4.8 months, CA 19-9: 14.2 vs 7.1 vs 5.2 months; P