Saif Muhammad Wasif
Department of Medicine and Cancer Center, Tufts Medical Center, Tufts University School of Medicine, 800 Washington Street, Box 245, Boston, MA 02111, USA.
Expert Rev Clin Pharmacol. 2014 Jul;7(4):487-98. doi: 10.1586/17512433.2014.910451.
Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, it continues to be a therapeutic challenge. Gemcitabine approved by FDA in 1997, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic agents have been compared against or combined with gemcitabine in randomized Phase III trials and no drug was shown to be superior to single-agent gemcitabine except FOLFIRINOX and nab-paclitaxel plus gemcitabine. On the other hand, efforts to integrate targeted agents such as BAY 12-9566, SCH 66336, bevacizumab, cetuximab, axitinib and sorafenib have been quite dismal despite extensive pre-clinical and clinical research over the last decade in the field of novel agents. To date, erlotinib remains the only biological agent that has demonstrated a small, but significant, added benefit to single agent gemcitabine. However, numerous new agents, including monoclonal antibodies and tyrosine kinase inhibitors, are currently being tested in an attempt to achieve better response, while maintaining a safe toxicity profile. In this article, the author discusses the management of advanced pancreatic and the current role of novel agents in this setting.
尽管我们对胰腺癌的分子和遗传基础的理解有所进步，但它仍然是一个治疗挑战。1997年被美国食品药品监督管理局（FDA）批准的吉西他滨，仅能适度改善肿瘤相关症状，且在生存方面只有微弱优势。在随机III期试验中，许多化疗药物已与吉西他滨进行比较或联合使用，除了FOLFIRINOX和纳米白蛋白结合型紫杉醇加吉西他滨外，没有药物显示优于单药吉西他滨。另一方面，尽管在过去十年中对新型药物领域进行了广泛的临床前和临床研究，但将靶向药物如BAY 12 - 9566、SCH 66336、贝伐单抗、西妥昔单抗、阿昔替尼和索拉非尼整合使用的努力一直很不理想。迄今为止，厄洛替尼仍然是唯一一种已证明对单药吉西他滨有小但显著附加益处的生物制剂。然而，目前正在测试许多新型药物，包括单克隆抗体和酪氨酸激酶抑制剂，以期在保持安全毒性特征的同时实现更好的反应。在本文中，作者讨论了晚期胰腺癌的治疗以及新型药物在这种情况下的当前作用。
