Oncology Frontier: Gastrointestinal perforation is a rare but serious adverse effect of bevacizumab. Can we identify that population which is at high risk for gastrointestinal perforation?

 

　　《肿瘤瞭望》：贝伐单抗是晚期结直肠癌的常用药物，有非常少见但极其严重的不良反应——胃肠穿孔。在您的经验中，或者据您了解，什么情况下出现胃肠穿孔的风险高？

 

　　Dr Kerr: It is an interesting question and it is a very rare side effect. In our QUASAR 2 trail， the patients treated with bevacizumab did not have an identifiably higher incidence of perforation. The side effects that we did find though were hypertension and an increased incidence of arterial thrombotic events. We have just done a genome-wide association study looking for germ line variance and we think that we have identified a couple of SNiPs which are small genetic mutations that may allow us to identify those patients most at risk for those side effects. This is another hot area of science whereby we would like to use genetic tests to identify patients most at risk for side effects so we can reduce the dose of the drug prior to treatment. This is a science we have called ‘toxgnostics’ and a topic we have just published in Nature Reviews Cancer. Most of the side effects from chemotherapy come in the first cycle. These side effects can be severe with an incidence of 30-40% of life-threatening side effects; even a toxic death rate of 1-2%. If we can do a simple genetic test that tells us which patients are most at risk， we can either reduce the dose of drug or in some cases， avoid it altogether. This could be a really important step forward.

 

　　Kerr教授: 这是个很有意思的问题，这也是个非常少见的不良反应。在我们的QUASAR 2试验中，采用贝伐单抗治疗的病人并没有确认的穿孔高发生率出现。我们的确发现的不良反应是高血压和动脉血栓事件发生率的增加。我们刚刚完成了一项寻找种系变异的全基因组关联研究，并且我们认为我们已经确认一对小遗传变异的SNiPs，这使我们能够鉴别出有发生这些不良反应风险的患者。这是另外一个热门领域，据此我们打算利用遗传测试确认有不良反应风险的患者，因而我们能在治疗之前减少给药剂量。这门科学我们称之为“Toxgnostics”，并且我们刚刚在Nature Reviews Cancer上提出了这个话题。化疗大多数不良反应出现在第一轮。这些不良反应很严重，大约30%～40%都是致命的不良反应，甚至毒性死亡率达到1%～2%。如果我们做一个简单的遗传测试就可以告诉我们哪些患者处于高危，那么在某些病例中减少药物剂量或许能完全避免不良反应。这可能是一项非常重要的进步。