Von Hoff Daniel D, Bearss David
Arizona Cancer Center, Tucson, Arizona 85724-5024, USA.
Curr Opin Oncol. 2002 Nov;14(6):621-7. doi: 10.1097/00001622-200211000-00006.
This past year has proved to be a relatively disappointing one for the development of agents that could improve the survival rates of patients with advanced pancreatic cancer. A well designed randomized trial of treatment of patients with gemcitabine with or without a farnesyl transferase inhibitor (tried because pancreatic cancers have a high incidence of K- abnormalities) showed no improvement in survival rates. A definitive randomized controlled trial with a histone deacetylase inhibitor also proved negative. There are some signs of hope in that in early nonrandomized studies there are some new agents that appear to have some activity against the disease. These agents include the thymidylate synthase inhibitor capecitabine (which is possibly activated at the tumor site), the antigastrin immunogen G17DT (which is an immunization designed to neutralize the pancreatic growth factor gastrin), and the topoisomerase I inhibitor 9-nitrocamptothecin. In addition, the combination of the new agent oxaliplatin to high-dose 5FU plus leucovorin, which gave a median survival rate of 12.5 months, is also worthy of further study. Supportive care findings of interest for the patient with advanced pancreatic cancer of note include: the study in which eicosapentaenoic acid (fish oil) caused a modest weight gain (median of 1 kg), and the finding that ofloxacin plus ursodeoxycholic acid was not superior to ursodeoxycholic acid alone for the prevention or occlusion of biliary stents.
过去一年对于研发能够提高晚期胰腺癌患者生存率的药物而言，是相对令人失望的一年。一项精心设计的随机试验，针对使用吉西他滨治疗的患者，对比了加用或不加用法尼基转移酶抑制剂（之所以进行此项试验，是因为胰腺癌中K-异常的发生率较高），结果显示生存率并未提高。一项关于组蛋白去乙酰化酶抑制剂的确定性随机对照试验也得到了阴性结果。不过，仍有一些希望的迹象，在早期非随机研究中，有一些新药物似乎对该疾病有一定活性。这些药物包括胸苷酸合成酶抑制剂卡培他滨（可能在肿瘤部位被激活）、抗胃泌素免疫原G17DT（一种旨在中和胰腺生长因子胃泌素的免疫制剂）以及拓扑异构酶I抑制剂9-硝基喜树碱。此外，新药物奥沙利铂与高剂量5-氟尿嘧啶加亚叶酸联合使用，中位生存率为12.5个月，这也值得进一步研究。对于晚期胰腺癌患者而言，值得关注的支持性治疗研究结果包括：一项研究表明，二十碳五烯酸（鱼油）可使患者体重适度增加（中位数为1千克）；还有一项研究发现，氧氟沙星加熊去氧胆酸在预防或阻塞胆管支架方面并不优于单独使用熊去氧胆酸。
