Nucleosomes, ProGRP, NSE, CYFRA 21-1, and CEA in monitoring first-line chemotherapy of small cell lung cancer

Stefan Holdenrieder, Joachim Von Pawel, Elke Dankelmann, Thomas Duell, Bernhard Faderl, Andreas Markus, Maria Siakavara, Horst Wagner, Knut Feldmann, Harald Hoffmann, Hannelore Raith, Dorothea Nagel, Petra Stieber

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96 Scopus citations


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.

Original languageEnglish
Pages (from-to)7813-7821
Number of pages9
JournalClinical Cancer Research
Issue number23
StatePublished - 1 Dec 2008
Externally publishedYes


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