Abstract
PURPOSE: The present study was designed to elucidate the fluctuation of activated CECs (aCECs) during different therapies and to investigate their predictive value for efficacy of anti-angiogenesis and chemotherapy in advanced non-small cell lung cancer (NSCLC). METHODS: Seventy-two patients were randomized into three arms, treated with concomitant NP (vinorelbine and cisplatin) and Rh-endostatin, Rh-endostatin followed by NP, and single NP up to a maximum of six cycles. Response, time to progression (TTP), and aCECs levels were observed. The correlation between aCECs and efficacy was analyzed. RESULTS: We found that TTP was 8.5 months in concomitant NP and Rh-endostatin versus 5.3 months in NP (p = 0.04) and 6.0 months in Rh-endostatin followed by NP. aCECs fluctuated during the therapeutic period, with a significantly high level from baseline on 8th day of Rh-endostatin followed by NP regimen, that is, when single Rh-endostatin was administered for 1 week, and upon completion of therapy in cases of progressive disease in each group (all p < 0.05). When TTP was longer than 10 months, aCECs count difference (∆aCECs, the difference in the aCECs by post-therapeutic amount minus pre-therapeutic amount) was reversely correlated to TTP (p = 0.003, r = -0.647). CONCLUSIONS: An improved synergistic effect was achieved from concomitant NP and Rh-endostatin compared with Rh-endostatin followed by NP and single NP. aCECs increased when the disease was aggravated or single Rh-endostatin treatment of Rh-endostatin was administered, while they decreased when a clinical response to the combined therapy was obtained. Our results suggest ∆aCECs as an ideal marker to predict the response to Rh-endostatin combined with chemotherapy.