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Circulating Nucleosomes Predict the Response to Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer
Ist Teil von
Clinical cancer research, 2004-09, Vol.10 (18), p.5981-5987
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2004
Quelle
MEDLINE
Beschreibungen/Notizen
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.