Recombinant human endostatin combined with radiotherapy in the treatment of brain metastases of non-small cell lung cancer

Abstract

Objective: Since brain metastases (BM) is often accompanied by edema, and endostatin (ES) can prevent tumor tissue edema, we investigated the therapeutic effects of ES combined with radiotherapy in the treatment of BM of NSCLC. We also determined the patients who are suitable for this therapy.

Methods: Eighty patients with BM of NSCLC were randomly divided into combination group and radiotherapy alone group. The primary endpoint was overall response rate, and secondary endpoints were overall survival time, cerebral edema index and adverse reactions. These were observed and the expressions of vascular endothelial growth factor receptor 2 (VEGFR2) protein and KDR gene in primary lesions were detected with immunohistochemical method and fluorescence in situ hybridization.

Results: Compared with radiotherapy alone, brain edema was significantly reduced in the ES group (P = 0.003) without marked adverse reactions. For the overall response rate, there was no statistical significant difference between the two groups (control, 90 % vs. ES, 75 %, P = 0.07), but there was statistical significance in the patients with positive VEGFR2 (93 vs. 67.7 %, P = 0.012) or positive KDR gene (94.4 vs. 47.3 %, P = 0.002). In overall survival time, there was no statistical significance in the two groups (P = 0.35), in the tumors with positive VEGFR2 (P = 0.109) or with positive KDR gene (P = 0.147).

Conclusion: Compared with radiotherapy alone, ES combined with radiotherapy can reduce brain edema in NSCLC patients with BM and obtain better short-term response rate in tumors with positive VEGFR2 or positive KDR gene, but does not improve the overall survival.