Prognostic and Predictive Value of Carcinoembryonic Antigen and Cytokeratin-19 Fragments Levels in Advanced Non-Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Purpose: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. Materials and Methods: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. Results: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. Conclusion: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.
Abstract
Purpose: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. Materials and Methods: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. Results: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. Conclusion: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.
참고문헌 (36)
- Jemal A, "Cancer statistics, 2008", CA Cancer J Clin, 58, pp.71~96 (2008)
- Shepherd FA, "Erlotinib in previously treated non-small-cell lung cancer", N Engl J Med, 353, pp.123~132 (2005)
- Kim ES, "Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial", Lancet, 372, pp.1809~1818 (2008)
- Mok TS, "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma", N Engl J Med, 361, pp.947~957 (2009)
- Maheswaran S, "Detection of mutations in EGFR in circulating lung-cancer cells", N Engl J Med, 359, pp.366~377 (2008)
- Molina R, "Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE", Tumour Biol, 29, pp.371~380 (2008)
- Okada M, "Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease", Ann Thorac Surg, 78, pp.216~221 (2004)
- Pujol JL, "Cyfra 21-1, neuron specific enolase and prognosis of non-small cell lung cancer: prospective study in 621 patients", Lung Cancer, 31, pp.221~231 (2001)
- Holdenrieder S, "Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer", Lung Cancer, 63, pp.128~135 (2009)
- Ardizzoni A, "Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer", Cancer, 107, pp.2842~2849 (2006)
- Okamoto T, "Serum carcinoembryonic antigen as a predictive marker for sensitivity to gefitinib in advanced non-small cell lung cancer", Eur J Cancer, 41, pp.1286~1290 (2005)
- Barlési F, "CYFRA 21-1 level predicts survival in non-small-cell lung cancer patients receiving gefitinib as third-line therapy", Br J Cancer, 92, pp.13~14 (2005)
- Chiu CH, "Serum tumor markers as predictors for survival in advanced non-small cell lung cancer patients treated with gefitinib", Lung Cancer, 57, pp.213~221 (2007)
- Travis WD, "Histological typing of lung and pleural tumours. 3rd ed" (1999), Springer-Verlag
- Therasse P, "New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada", J Natl Cancer Inst, 92, pp.205~216 (2000)
- 한세원, "Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib", JOURNAL OF CLINICAL ONCOLOGY, 23, pp.2493~2501, AMER SOC CLINICAL ONCOLOGY
- Gold P, "Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques", J Exp Med, 121, pp.439~462 (1965)
- Fujishima T, "Increased carcinoembryonic antigen concentrations in sera and bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis", Respiration, 62, pp.317~321 (1995)
- Rule AH, "Tumor-associated (CEA-reacting) antigen in patients with inflammatory bowel disease", N Engl J Med, 287, pp.24~26 (1972)
- Okada M, "Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non-small cell lung carcinoma", Ann Thorac Surg, 78, pp.1004~1009 (2004)
- Matsuoka K, "Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stage I non-small cell lung cancer", Eur J Cardiothorac Surg, 32, pp.435~439 (2007)
- Shoji F, "Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas", Cancer, 110, pp.2793~2798 (2007)
- Benchimol S, "Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule", Cell, 57, pp.327~334 (1989)
- Hammarström S., "The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues", Semin Cancer Biol, 9, pp.67~81 (1999)
- Screaton RA, "Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation", J Cell Biol, 137, pp.939~952 (1997)
- Ordoñez C, "Human carcinoembryonic antigen functions as a general inhibitor of anoikis", Cancer Res, 60, pp.3419~3424 (2000)
- Stieber P, "Cytokeratin 19 fragments: a new marker for non-small-cell lung cancer", Clin Biochem, 26, pp.301~304 (1993)
- Nisman B, "Evaluation of tissue polypeptide specific antigen, CYFRA 21-1, and carcinoembryonic antigen in nonsmall cell lung carcinoma: does the combined use of cytokeratin markers give any additional information?", Cancer, 82, pp.1850~1859 (1998)
- Barlési F, "Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer", Respir Med, 98, pp.357~362 (2004)
- Pujol JL, "CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients", Br J Cancer, 90, pp.2097~2105 (2004)
- Kao CH, "Cytokeratin fragment 19 (CYFRA 21-1) in healthy smokers", Anticancer Res, 19, pp.4545~4546 (1999)
- Molina R, "Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors", Tumour Biol, 24, pp.209~218 (2003)
- Shigematsu H, "Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers", J Natl Cancer Inst, 97, pp.339~346 (2005)
- Gaughan EM, "Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities", Ther Adv Med Oncol, 3, pp.113~125 (2011)
- Shaw AT, "Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis", Lancet Oncol, 12, pp.1004~1012 (2011)
- Herbst RS, "Sorafenib treatment efficacy and KRAS biomarker status in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial", J Clin Oncol, 28(15 Suppl), pp.7609~ (2010)