Bendell Johanna, Goldberg Richard M
Duke University Medical Center, North Carolina, USA.
Curr Opin Oncol. 2007 Jul;19(4):390-5. doi: 10.1097/CCO.0b013e32816f76f0.
The treatment of pancreatic cancer is an ongoing challenge with minimal substantive improvement in patient outcomes despite many randomized phase III clinical trials evaluating multiple agents, both alone and in combination. Such disappointing outcomes clearly call for broadening the scope of pharmacologic approaches to managing this disease. With increasing insight into pathways within tumor cells that are related to tumor growth and spread, and development of 'targeted therapies' against these pathways, much attention has turned to the use of these agents, alone or coupled with chemotherapy, in the treatment of pancreatic cancer.
Several targeted agents have been studied in patients with pancreatic cancer. Of the agents studied, the only agent that has shown to provide a modest but significant benefit in survival for these patients is erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.
From trials done to date, minimal benefit has been found with the addition of targeted agents in the treatment of pancreatic cancer. More potential pathways remain to be targeted, however, and there are a plethora of new agents to be tested. Due to the likelihood that different pathways drive the development and growth of different tumors of the same site of origin the inclusion of biomarker studies to correlate with treatment effect may be a necessary component of clinical trials to learn how to best tailor therapy to the patient.
尽管有许多评估多种药物单独或联合使用的随机III期临床试验,但胰腺癌的治疗仍然是一项持续的挑战,患者预后的实质性改善微乎其微。如此令人失望的结果显然需要拓宽管理这种疾病的药理学方法范围。随着对肿瘤细胞内与肿瘤生长和扩散相关途径的深入了解,以及针对这些途径的“靶向治疗”的发展,人们的注意力已转向单独或与化疗联合使用这些药物来治疗胰腺癌。
已在胰腺癌患者中研究了几种靶向药物。在研究的药物中,唯一显示对这些患者的生存有适度但显著益处的药物是厄洛替尼,一种表皮生长因子受体酪氨酸激酶抑制剂。
从迄今为止进行的试验来看,在胰腺癌治疗中添加靶向药物的益处微乎其微。然而,仍有更多潜在途径有待靶向,并且有大量新药有待测试。由于不同途径可能驱动同一起源部位不同肿瘤的发生和生长,纳入生物标志物研究以与治疗效果相关联可能是临床试验的必要组成部分,以便了解如何最好地为患者量身定制治疗方案。