分子靶向药物在胃肠道肿瘤综合治疗中的应用

Application of molecular targeted agents in comprehensive treatment of gastrointestinal cancer

分子靶向药物在晚期胃肠道肿瘤治疗中,被证实可提高患者的客观缓解率并延长总生存期.因此,其在局部进展期胃肠道肿瘤综合治疗中的价值被逐渐重视.曲妥珠单抗用于HER-2基因阳性的局部进展期胃癌新辅助化疗中的临床研究正在进行中,结果值得期待.大量研究证明,西妥昔单抗联合化疗对于KRAS基因野生型潜在可切除的结直肠癌肝转移患者,能提高手术切除率并延长总生存期;而贝伐珠单抗在KRAS基因突变型结直肠癌肝转移术前转化治疗中的作用正在评估中.对于可切除的结直肠癌肝转移,虽现有的证据显示,分子靶向药物在新辅助治疗中未能带来长期生存益处,但最终结论仍存议甚多.对于局部进展期直肠癌患者,新辅助化疗中的西妥昔单抗在二期临床研究中未能显示治疗获益,贝伐珠单抗的作用同样需要在三期临床研究后进一步证实.与晚期肿瘤单一治疗模式不同,在肿瘤综合治疗中,需要系统评估分子靶向药物与细胞毒药物、手术以及放疗之间可能的相互影响及协同作用,制定出科学并适用于临床实践的综合治疗模式.

Targeted agents increase response rates and improved overall survival in treatment of metastatic gastrointestinal cancer.Therefore,physicians pay more attention to the role of targeted agents in treatment of local advanced gastrointestinal cancer.The clinical trials are ongoing to evaluate the efficacy of Trastuzumab in neoadjuvant treatment of local advanced gastric cancer with HER-2 gene over expression.Many studies reported Cetuximab plus chemotherapy as a conversion treatment improve R0 resection rates and prolonged overall survival of the patients with potentially resectable colorectal cancer liver metastasis with wild type KRAS gene status.A phase Ⅲ clinical trial is assessing the conversion efficacy of Bevacizumab in unresectable disease with KRAS gene mutation.Current evidence showed that neoadjuvant therapy of targeted agents did not prolong survival of patients with resectable liver metastasis.However,this is controversial.In neoadjuvant therapy of local advanced rectal cancer,Cetuximab did not improve the rates of pathological complete response in most of the phase Ⅱ trials.Furthermore,there are no phase Ⅲ trials to assess the role of Bevacizumab.Compared to chemotherapy alone for metastatic cancer,it is more important to evaluate the interaction and synergistic action of targeted agents,cytotoxic drugs,surgery and radiation,to make a scientific multidisciplinary model in comprehensive treatment of local advanced cancer.