OBJECTIVETo observe the correlation between long term efficacy/safety and treatment cycles of rh-endostatin (endostar) combined with TP (paclitaxel plus cisplatin/carboplatin) or NP (navelbine plus cisplatin/carboplatin) regimens in patients with advanced non-small cell lung cancer (NSCLC).

METHODSTwenty-five patients with advanced NSCLC confirmed by histopathology and/or cytology were enrolled in this study. Twenty-one patients underwent endostar combined with NP regimen and other four patients underwent endostar combined with TP regimen (all repeated 21 days) treatment. The therapeutic effects, quality of life (QOL) and adverse effects were evaluated according to RECIST criteria, Karnofsky performance scores and WHO grading of adverse effects, respectively. Our intention was to make knowledge of the therapeutic effects, median time to progression, one-year survival rate, median overall survival and adverse reactions. The amount of circulating endothelial cells (CEC) in peripheral blood was measured by flow cytometry.

RESULTSAll the 25 patients were evaluable for efficacy and safety. They were comprised of 5 cases of PR, 14 cases of SD and 6 cases of PD. Of the 25 cases, RR was obtained in 5 cases (20.0%), CBR in 19 cases (76.0%), mTTP was 8 months and mOS was 19 months. Of the 14 patients with short treatment cycles (< 4), PR was obtained in 2 cases, SD in 6 cases and PD in 6 cases, RR was 14.3%. Of the 8 patients who obtained PR or SD, the median TTP was 6 months and median overall survival was 18 months. Of the 11 patients with long treatment cycles (≥ 4), PR was obtained in 3 cases, SD in 8 cases, RR was 27.3%, mTTP was 17 months and mOS was 26 months. After treatment, the amount of activated CECs was increased by (293 ± 12)/10(5) in patients with short treatment cycles, and decreased by (243 ± 181)/10(5) in patients with long treatment cycles. A positive correlation was found between the changes of activated CECs after therapy, time to progression (TTP) and treatment cycles (r = 0.970, P = 0.001; r = 0.829, P = 0.042, respectively). The quality of life (QOL) was improved in 12 cases (48.0%), stable in 10 cases (40.0%), and decreased in 3 cases (12.0%). Grade 3 and 4 toxicities were mainly related with chemotherapeutics, including neutropenia in 4 cases (16.0%), vomiting in 3 cases (12.0%) and arrhythmia in 1 case. No hypertension was observed. All the adverse reactions did not affect the following treatment, and there was no significant difference in incidence rate of grade 3 and 4 adverse events between the patients treated with long-term and short-term cycles.

CONCLUSIONSEndostar combined with TP or NP regimen chemotherapy is effective and safe in the treatment of advanced NSCLC, especially in patients with long term treatment cycles which can effectively prolong TTP and reach long term survival, but not increase adverse events. The QOL of patients can be improved or remain stable. The changes of CECs may be used as a useful maker in predicting the efficacy of the combination treatment.