Stathopoulos George P, Androulakis Nikos, Souglakos John, Stathopoulos John, Georgoulias Vassilis
First Department of Oncology, Errikos Dunant Hospital, Athens, Greece.
Anticancer Res. 2008 Mar-Apr;28(2B):1303-8.
Advanced or metastatic pancreatic cancer is an incurable disease. The main treatment is chemotherapy with cytotoxic agents. On the basis of our experience in clinical trials, the objectives have been to determine response rate, life prolongation and clinical benefit. In our trials and in those of other authors, all of these objectives have been met. Responses remain low; 5-25% of patients have a partial response, life prolongation is significantly achieved versus best supportive care, and clinical benefit is observed in 40-60% of patients. Rarely do patients survive for over 2 years and no patient is cured. The standard cytotoxic treatment is the agent gemcitabine. The addition of other agents, such as cisplatin, irinotecan, oxaliplatin and taxanes, in combination with gemcitabine, has shown higher response rates but overall survival has not significantly increased. Research related to monoclonal or gene therapies for pancreatic cancer has created hope. The horizon has been broadened by a recent report on a tyrosine kinase inhibitor, erlotinib (EGFR inhibitor) which has shown significantly longer median survival, when combined with gemcitabine versus gemcitabine alone. Other anti-angiogenic agents, such as cetuximab and the anti-Her-2, herceptin, are now being tested in ongoing trials. Farnesyl transferase inhibitors represent another direction which research is taking; this is related to the Ras-oncogenes (K-, H- and N-ras) which are known to be involved in signal transduction pathways regulating cell growth and differentiation in many human cancers including pancreatic. Trials of these and other targeting therapies have not produced the expected effectiveness. The combination of monoclonal and/or gene therapies with cytotoxic agents suggests there is hope for the future.
晚期或转移性胰腺癌是一种无法治愈的疾病。主要治疗方法是使用细胞毒性药物进行化疗。根据我们在临床试验中的经验，目标是确定缓解率、延长生存期和临床获益情况。在我们的试验以及其他作者的试验中，所有这些目标均已达成。缓解率仍然较低；5%至25%的患者有部分缓解，与最佳支持治疗相比，生存期显著延长，并且40%至60%的患者观察到临床获益。患者很少能存活超过2年，且无患者被治愈。标准的细胞毒性治疗药物是吉西他滨。将其他药物，如顺铂、伊立替康、奥沙利铂和紫杉烷与吉西他滨联合使用，已显示出更高的缓解率，但总生存期并未显著增加。与胰腺癌的单克隆或基因治疗相关的研究带来了希望。最近一份关于酪氨酸激酶抑制剂厄洛替尼（表皮生长因子受体抑制剂）的报告拓宽了视野，该抑制剂与吉西他滨联合使用时，与单独使用吉西他滨相比，中位生存期显著延长。其他抗血管生成药物，如西妥昔单抗和抗Her-2药物赫赛汀，目前正在进行的试验中接受测试。法尼基转移酶抑制剂代表了研究的另一个方向；这与Ras癌基因（K-、H-和N-Ras）有关，已知这些癌基因参与调节包括胰腺癌在内的许多人类癌症中细胞生长和分化的信号转导通路。这些以及其他靶向治疗的试验尚未产生预期的效果。单克隆和/或基因治疗与细胞毒性药物的联合使用表明未来仍有希望。
