e18088 Background: Combinations of anti-angiogenic drugs with chemotherapeutics are widely used for cancers control. Whether can better efficacy of such a combinated modality be achieved and predicted earlier is a great challenge. Circulating endothelial cells (CECs) and cytokeratins (CKs) might have a role in tumour angiogenesis and in tumour cell death. Measurement of CECs and CKs in the blood of patients with tumors could be a simple, non-invasive approach to monitor or predict responses and survival to treatment. Methods: One hundred and seven patients with primary advanced non-small cell lung cancer (NSCLC) were enrolled, randomly assigned to either the endostatin treatment group (paclitaxel+ carboplatin+ endostatin) or the control group (paclitaxel+carboplatin). CEC count and serum CK8, caspase-cleaved CK18 (ccCK18) and uncleaved CK18 (CK18) were measured in the 107 subjects at before treatment (baseline), week 3, and week 6 of treatment, respectively. Results: Higher baseline CEC count was observed in patients with good tumor response (p=0.002 for all the 107 patents; p=0.000 in the treatment group). When compared with the baseline level, after 6 weeks therapy in the endostatin group, CECs decreased significantly (p=0.000), but the CKs levels increased. The increased levels of ccCK18 and CK18 at week 6 reached significance in the treatment group (p=0.001 and p=0.048, respectively). Tumor response showed strong correlation with the reduction extent of CECs (p=0.000) and the increase value of ccCK18 (p=0.040) after endostatin therapy. The best cut-off values of the changes of CECs and ccCK18 for prediction of survival were designed being 0.58/ul and 19.6ng/ml, respectively. Furthermore, obvious reduction of CECs and more rise of ccCK18 significantly correlated with the longer median survival (p= 0.013 and p = 0.016 for PFS, p = 0.009 and p=0.012 for OS, respectively). Conclusions: CECs and CKs would be the impressive biomarkers to explore for selecting NSCLC patients who might benefit from endostain in combination with paclitaxel plus carboplatin treatment.
Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy
