CYFRA 21-1 as a Prognostic and Predictive Marker in Advanced Non–Small-Cell Lung Cancer in a Prospective Trial: CALGB 150304

Background: Cytokeratin 19 and its soluble fragment CYFRA have been studied as markers that may be associated with response to therapy and survival in non–small-cell lung cancer (NSCLC). As a prospective correlative study of Cancer and Leukemia Group B 30203, a randomized phase II trial of carboplatin/gemcitabine with eicosanoid modulators (celecoxib, zileuton, or both) in advanced NSCLC, serum CYFRA levels were obtained before and during treatment. Methods: Serum CYFRA levels were measured at baseline and after the first cycle of treatment using an electrochemoluminescent assay. Paired specimens were available from 88 patients. The logarithms of the initial concentration and of the difference in concentrations were analyzed for association with overall survival (OS) and failure-free survival (FFS). Results: Lower baseline CYFRA levels were associated with both longer OS and FFS (p < 0.0001 and p = 0.0003). In addition, larger reductions in CYFRA levels correlated with longer OS and FFS (p = 0.0255 and p = 0.0068). Conclusion: CYFRA and change in CYFRA were found to be reliable markers for response to chemotherapy for NSCLC; however, a precise threshold to mark response has yet to be determined.

[1]  Isaac Nuñez,et al.  Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC). , 2011, Clinical lung cancer.

[2]  Carl Morrison,et al.  Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy--Cancer and Leukemia Group B Trial 30203. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  P. Bakakos,et al.  Carcinoembryonic antigen, neuron‐specific enolase and cytokeratin fragment 19 (CYFRA 21‐1) levels in induced sputum of lung cancer patients , 2008, Scandinavian journal of clinical and laboratory investigation.

[4]  T. Peretz,et al.  Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer: association of marker changes after two chemotherapy cycles with different measures of clinical response and survival , 2007, British Journal of Cancer.

[5]  H. Satoh,et al.  Preoperative CYFRA 21-1 levels as a prognostic factor in c-stage I non-small cell lung cancer. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[6]  A. Ardizzoni,et al.  Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer , 2006, Cancer.

[7]  K. Feldmann,et al.  Early and Specific Prediction of the Therapeutic Efficacy in Non–Small Cell Lung Cancer Patients by Nucleosomal DNA and Cytokeratin‐19 Fragments , 2006, Annals of the New York Academy of Sciences.

[8]  Jin H. Lee,et al.  Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments in patients with effusions from primary lung cancer. , 2005, Chest.

[9]  D. Caillaud,et al.  Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients. , 2004, The International journal of biological markers.

[10]  J. Mancini,et al.  Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer. , 2004, Respiratory medicine.

[11]  B. Jeremic,et al.  Comparison of serum growth factors and tumor markers as prognostic factors for survival in non-small cell lung cancer. , 2003, Anticancer research.

[12]  H. Dienemann,et al.  Increased CYFRA 21-1 and CEA levels are negative predictors of outcome in p-stage I NSCLC. , 2003, Anticancer research.

[13]  D. Ferrigno,et al.  Clinical equivalence of two cytokeratin markers in mon-small cell lung cancer: a study of tissue polypeptide antigen and cytokeratin 19 fragments. , 2003, Chest.

[14]  R. Govindan,et al.  Serum CYFRA 21-1 in advanced stage non-small cell lung cancer: an early measure of response. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  J. Kulpa,et al.  Carcinoembryonic antigen, squamous cell carcinoma antigen, CYFRA 21-1, and neuron-specific enolase in squamous cell lung cancer patients. , 2002, Clinical chemistry.

[16]  N. Siafakas,et al.  Prognostic Value of Serum Tumor Markers in Patients with Lung Cancer , 2002, Respiration.

[17]  D. Karnak,et al.  Evaluation of Cyfra 21-1: A Potential Tumor Marker for Non-Small Cell Lung Carcinomas , 2014, Lung.

[18]  M. Kosacka,et al.  Comparison of cytokeratin 19 expression in tumor tissue and serum CYFRA 21-1 levels in non-small cell lung cancer. , 2009, Polskie Archiwum Medycyny Wewnetrznej.

[19]  S. Ho,et al.  Monitoring Cytokeratin Fragment 19 (CYFRA 21-1) Serum Levels for Early Prediction of Recurrence of Adenocarcinoma and Squamous Cell Carcinoma in the Lung after Surgical Resection , 2002, Lung.