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


METHODS
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.
Holdenrieder
Stefan
S
Institute of Clinical Chemistry, University Hospital Munich, Munich, Germany. Stefan.Holdenrieder@med.uni-muenchen.de
von Pawel
Joachim
J
Dankelmann
Elke
E
Duell
Thomas
T
Faderl
Bernhard
B
Markus
Andreas
A
Siakavara
Maria
M
Wagner
Horst
H
Feldmann
Knut
K
Hoffmann
Harald
H
Raith
Hannelore
H
Nagel
Dorothea
D
Stieber
Petra
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D053539:Keratin-19; D007633:Keratins / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes; D010446:Peptide Fragments / Q000097:blood*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011379:Prognosis; D012372:ROC Curve; D011994:Recombinant Proteins / Q000097:blood; D012680:Sensitivity and Specificity; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D009707:Nucleosomes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C102012:antigen CYFRA21.1; C087079:pro-gastrin-releasing peptide (31-98); D007633:Keratins; D010751:Phosphopyruvate Hydratase