Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
Thromb Res. 2012 Apr;129 Suppl 1:S50-3. doi: 10.1016/S0049-3848(12)70016-6.
Anti-angiogenic drugs and in particular anti-vascular endothelial growth factor (VEGF) agents have entered the clinical armamentarium against cancer. New unexpected toxicities have emerged. The incidence and the severity of these toxicities have a great variability in the different studies. Among them, bleeding is one of the most severe and difficult to manage. Bevacizumab retains the highest frequency of bleeding complications, in particular epistaxis, hemoptysis and gastrointestinal bleeding. Although a higher incidence of severe hemorrhages has not been consistently demonstrated during the treatment with bevacizumab, mild bleeding episodes appear clearly increased in the experimental arm of most trials. Cases of severe pulmonary hemorrhage were reported in patients with lung cancer; these events occurred mainly intra-tumor and were significantly associated with squamous cell histology. Trials with other small-molecule tyrosine kinase inhibitors like sunitinib or sorafenib showed an overall lower rate of bleeding complications, but still significantly higher than the control arm in many cases. The mechanisms of bleeding induced by anti-VEGF agents are complex and not yet fully clarified: the main hypothesis is that VEGF could promote endothelial cell survival and integrity in the adult vasculature and its inhibition may decrease the renewal capacity of damaged endothelial cells. Management of bleeding in patients treated with anti-VEGF agents is a challenging task because this complication is at least in part inherent to the efficacy of the drug and because there is also an increased risk of thrombosis, both arterial and venous. So far, only few preliminary data are available on a strategy to prevent hemorrhage and thrombotic event.
抗血管生成药物，特别是抗血管内皮生长因子（VEGF）药物已被应用于癌症的临床治疗中。新的意外毒性作用也逐渐显现出来。这些毒性作用的发生率和严重程度在不同的研究中差异很大。其中，出血是最严重和最难处理的毒性作用之一。贝伐珠单抗保留了最高频率的出血并发症，特别是鼻出血、咯血和胃肠道出血。虽然在贝伐珠单抗治疗期间并未一致证明严重出血的发生率更高，但在大多数试验的实验组中，轻度出血事件显然明显增加。肺癌患者报告了严重肺出血的病例；这些事件主要发生在肿瘤内，与鳞状细胞组织学显著相关。其他小分子酪氨酸激酶抑制剂如舒尼替尼或索拉非尼的试验显示出血并发症的总体发生率较低，但在许多情况下仍明显高于对照组。抗 VEGF 药物引起出血的机制很复杂，尚未完全阐明：主要假设是 VEGF 可促进成年血管内皮细胞的存活和完整性，其抑制可能会降低受损内皮细胞的更新能力。抗 VEGF 药物治疗患者的出血管理是一项具有挑战性的任务，因为这种并发症至少部分是药物疗效所固有的，而且还存在动脉和静脉血栓形成的风险增加。到目前为止，关于预防出血和血栓事件的策略仅有少量初步数据。
