Abstract 2984: Normalization of tumor vasculature by anti-angiogenesis therapy in metastatic tumor: A clinical study to determine the timing and effect

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Clinically, combination of anti-angiogenic agents with chemotherapeutic agents demonstrated better antitumor efficacy. Instead of merely effect on vasculature regression, careful use of anti-angiogenic therapy may cause the grossly abnormal structure and function of tumor blood vessels to return to a more normal state. Treatment with anti-angiogenic agents can primarily improve chemotherapy efficacy by normalizing tumor vasculature, decrease the intra-tumor interstitial pressure, thereby leading to a more effective drug delivery. We planned to investigate the timing and effect of tumor vascular normalization in human after the administration of anti-angiogenic agent. It may help determine the appropriate timing of administration of chemotherapeutic agents after anti-angiogenic treatment. Materials and methods: This study enrolled the last 8 consecutive patients who participated in a phase II trial for treatment of refractory brain metastases from breast cancer (Eur J Can 49:2s, 2013 suppl; abstr 1878). The protocol treatment consists of bevacizumab 15mg/kg on day 1, chemotherapy of etoposide and cisplatin on day 2 (24 hours after administration of bevacizumab), in 21-day cycles. These 8 patients specifically received four dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations. DCE-MRI was performed before treatment, 1 hour after the end of bevacizumab infusion (i.e., 2.5 hours after starting bevacizumab infusion), 24 hours and 21 days after bevacizumab infusion. This study was registered with ClinicalTrials.gov, identifier [NCT01281696][1], and was approved by the ethical review board. Results: Clinically, all the 8 patients achieved partial remission at central nervous system. All of the 4 DCE-MRI parameters decreased after bevacizumab infusion. Compared to baseline values, the mean reductions at 1 hour and 24 hours were -12.8% and -24.7% for Peak, -46.6% and -65.8% for Slope, -27.9% and -55.5% for iAUC60, -46.6% and -63.9% for Ktrans, respectively (all P values <0.05). The differences between 1 hour and 24 hours reached statistical significance (all P values <0.05) for all the parameters. However, the differences in the mean percentage change between 24 hours and 21 days did not reach significance in any of the four parameters Conclusion: Normalization of tumor vasculature induced by bevacizumab was clearly demonstrated in brain metastases in human at 1 hour after completion of bevacizumab infusion, but significantly became more obvious at 24 hours after bevacizumab administration. Citation Format: Yen-Shen Lu, Bang-Bin Chen, Ching-Hung Lin, Wei-Wu Chen, Pei-Fang Wu, Ann-Lii Cheng, Tiffany Ting-Fang Shih. Normalization of tumor vasculature by anti-angiogenesis therapy in metastatic tumor: A clinical study to determine the timing and effect. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2984. doi:10.1158/1538-7445.AM2014-2984 [1]: /lookup/external-ref? link_type=CLINTRIALGOV&access_num=NCT01281696&atom=%2Fcanres%2F74%2F19_Supplement%2F2984.atom