Circulating Nucleosomes Predict the Response to Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer

• Published in: Clinical cancer research 2004-09, Vol.10 (18), p.5981-5987
• Main Authors: HOLDENRIEDER, Stefan, STIEBER, Petra, VON PAWEL, Joachim, RAITH, Hannelore, NAGEL, Dorothea, FELDMANN, Knut, SEIDEL, Dietrich
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - blood; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Carcinoembryonic Antigen - biosynthesis; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Drug Resistance, Neoplasm; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratin-19; Keratins - metabolism; Kinetics; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Multivariate Analysis; Nucleosomes - metabolism; Pharmacology. Drug treatments; Time Factors; Treatment Outcome; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0625

Purpose: We investigated the potential of circulating, nucleosomal DNA for the early prediction of the efficacy of chemotherapy in patients with advanced lung cancer. Experimental Design: In serum of 212 patients with newly diagnosed non–small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before each new therapeutic cycle. Additionally, carcinoembryonic antigen and cytokeratin 19 fragments (CYFRA 21–1; Elecsys, Roche) were determined before each cycle. The therapeutic success was classified by computed tomography before start of the third cycle according to the World Health Organization criteria. Results: In univariate analysis, responders (patients with remission) showed significantly ( P < 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1–8) of nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3 (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to 2 (BV1–2) and from cycle 1 to 3 (BV1–3) compared with nonresponders (patients with stable or progressive disease). Additionally, CYFRA 21–1 (BV1, BV2, BV3, BV1–2, BV1–3) and carcinoembryonic antigen (BV1–2) discriminated significantly between both groups. In multivariate analysis including all parameters available until end of the first therapeutic cycle, nucleosomes (AUC 1–8), CYFRA 21–1 (BV1), stage, and age were independent predictors of therapy response with nucleosomes (AUC 1–8) having the strongest impact. Conclusion: Circulating nucleosomes in combination with oncological biomarkers are valuable for the early estimation of the efficacy of chemotherapy in patients with lung cancer.