Serological cell death
biomarkers and
circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death
biomarkers in patients with
small cell lung cancer. Blood samples from 88 patients were assayed using
enzyme-linked
immunosorbent assays for various
cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal
DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death
biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30, M65,
lactate dehydrogenase, and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis, both
lactate dehydrogenase and M65 levels remained significant. CTC number fell following
chemotherapy, whereas levels of serological cell death
biomarkers peaked at 48 hours and fell by day 22, mirroring the
tumor response. A 48-hour rise in nucleosomal
DNA and M30 levels was associated with early response and severe toxicity, respectively. Our results provide a rationale to include the use of serological
biomarkers and CTCs in early clinical trials of new agents for
small cell lung cancer.