法国南特大学医学院、R. Gauducheau综合肿瘤中心Jean-Yves Douillard教授访谈

　　Jean-Yves Douillard   法国南特大学医学院、R. Gauducheau综合肿瘤中心肿瘤内科学教授，ESMO教育委员会现任主席。他参与了肺癌和消化道的多项临床试验，对包括长春瑞滨、伊立替康、多西他赛、紫杉醇和吉西他滨等在内的多种新药进行了研究，同时还对吉非替尼、埃罗替尼、法尼基转移酶抑制剂、Raf激酶抑制剂、抗血管生成分子和单克隆抗体等靶向治疗药物进行了研究，在多本顶尖肿瘤学杂志上发表了大量文章。在第17届全国临床肿瘤学大会暨2014年CSCO学术年会的ESMO-CSCO联合论坛上，Douillard教授与徐瑞华教授共同主持了有关结直肠癌的进展讨论，并发表专题演讲。会后《肿瘤瞭望》就EGFR抑制剂联合化疗的不良反应管理和疗效预测，对Douillard教授进行了采访。

　　Oncology Frontier: What’s the serious adverse effect of EGFR inhibitors in combination with chemotherapy?

　　《肿瘤瞭望》：表皮生长因子受体（EGFR）抑制剂联合化疗的严重不良影响是什么？

　　Dr Douillard: When anti-EGFR antibodies are used in conjunction with chemotherapy， there will be the toxicity of the chemotherapy plus the specific side effects of the anti-EGFR. The main side effect of the anti-EGFRs which are due to receptor distribution， is skin toxicity. Skin toxicity occurs in at least 80% of patients. It is worth noting that patients that develop skin toxicity quite often have a better outcome than the patients without skin toxicity. It is generally grade 1 (mild) or grade 2 (moderate) in most cases with the exception of grade 3 (severe). It can be improved with local skin therapy but will progressively decrease with duration of treatment. The second most frequent side effect is diarrhea. Diarrhea is quite easy to manage but again， this toxicity is added on top of chemotherapy. For patients， the most striking side effect is skin toxicity because of course it has an impact on social life.

　　Douillard博士：EGFR抑制剂与化疗联合使用，会出现化疗毒性和抗EGFR的特异性副作用。EGFR抑制剂的副作用主要是皮肤毒性，与受体的分布情况有关。用药后，至少80％的患者会发生皮肤毒性反应。值得一提的是，发生皮肤毒性反应的患者往往比无皮肤毒性反应的患者治疗效果好。皮肤毒性反应在多数情况下，通常为1级（轻度）或2级（中度）反应，只有在极少数情况下发生3级（重度）反应。通过局部皮肤治疗可以得到改善，但随着治疗时间延长，疗效会降低。第二个最常见的副作用是腹泻。腹泻很容易处理，但是再次发生，将产生严重的化疗毒性。对于病人来说，最引人注意的副作用是皮肤的毒性，因为这对社会生活有影响。

　　Oncology Frontier: Could RAS mutation patients benefit from the combination of EGFR inhibitors and chemotherapy?

　　《肿瘤瞭望》：RAS基因突变患者能从EGFR抑制剂联合化疗中受益吗？

　　Dr Douillard: The answer is no. Any patient with a RAS mutation， either KRAS or NRAS， should not be treated with anti-EGFR monoclonal antibodies. There is either no  benefit or even a proven detrimental effect especially when used in combination with oxaliplatin.

　　Douillard博士：答案是否定的。任何发生RAS基因突变患者，无论是KRAS还是NRAS，都不应该用EGFR单克隆抗体治疗，既不能给患者带来获益，更甚的是，与奥沙利铂联合使用时，已证实会产生不利作用。。

　　Oncology Frontier: Are RAS mutations predictive biomarkers for anti-EGFR therapy?

　　《肿瘤瞭望》：RAS基因突变能作为抗EGFR治疗的生物学标志吗？

　　Dr Douillard: Yes. The knowledge of the RAS phenotype in terms of mutation is important information in order to decide on the treatment regimen. The patient presenting with no RAS metastasis get a lot of benefit from the addition of anti-EGFR monoclonal antibodies to chemotherapy. On the other hand， the existence of RAS mutation is a negative predictive factor of efficacy. In a patient with any RAS mutation， anti-EGFR should not be used.

　　Douillard博士：是的。RAS表型突变相关知识是决定治疗方案的重要信息。没有RAS转移的患者能从表皮生长因子受体单克隆抗体联合化疗中获益。另一方面，RAS突变的存在是疗效阴性的预测因子。对于任何RAS突变的患者，不宜使用抗EGFR治疗。