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Nucleosomes, ProGRP, NSE, CYFRA 21-1, and CEA in Monitoring First-Line Chemotherapy of Small Cell Lung Cancer

Authors' Affiliations: ¹ Institute of Clinical Chemistry, University Hospital Munich, Munich, Germany and ² Department of Oncology and ³ Institute of Laboratory Medicine, Asklepios Lung Hospital, Gauting, Germany

Requests for reprints: Stefan Holdenrieder, Institute of Clinical Chemistry, University Hospital Munich, Grosshadern Marchioninistr. 15, D-81366 Munich, Germany. Phone: 49-89-7095-3231; Fax: 49-89-7095-6298; E-mail: Stefan.Holdenrieder{at}med.uni-muenchen.de.

Purpose: Besides new therapeutic drugs, effective diagnostic tools indicating early the efficacy of therapy are required to improve the individual management of patients with nonoperable cancer diseases.

Experimental Design: In prospectively collected sera of 128 patients with newly diagnosed small cell lung cancer receiving first-line chemotherapy, the courses of nucleosomes, progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), and carcinoembryonic antigen were investigated and correlated with therapy response objectified by computed tomography before start of the third treatment course.

Results: In univariate analyses, high levels and insufficient decreases of nucleosomes, ProGRP, NSE, and CYFRA 21-1 during the first and second cycles of therapy correlated with poor outcome. Insufficient response to therapy was most efficiently indicated by the baseline values of nucleosomes, ProGRP, and CYFRA 21-1 before the second therapy cycle reaching areas under the curve (AUC) of 81.8%, 71.3%, and 74.9% in receiver operating characteristic curves, respectively. Combinations of nucleosomes with ProGRP (AUC 84.1%), CYFRA 21-1 (AUC 82.5%), and NSE (AUC 83.6%) further improved the diagnostic power in the high specificity range and yielded sensitivities of 47.1%, 35.3%, and 35.3% at 95% specificity, respectively. In multivariate analyses, including clinical and biochemical variables, only performance score and nucleosomes before cycle 2 were found to independently indicate therapy response.

Conclusions: Biochemical markers specifically identified patients with insufficient therapy response at the early treatment phase and showed to be valuable for diseases management of small cell lung cancer.