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优胜配方:紫杉醇在胰腺癌中的研发。

The winning formulation: the development of paclitaxel in pancreatic cancer.

机构信息

Authors' Affiliations: Roswell Park Cancer Institute, Buffalo, New York; and Centro Nacional de Investigaciones Oncologicas and Hospital de Madrid, Madrid, Spain.

出版信息

Clin Cancer Res. 2013 Oct 15;19(20):5572-9. doi: 10.1158/1078-0432.CCR-13-1356. Epub 2013 Aug 5.

Abstract

Paclitaxel has wide application in anticancer therapy but was never considered an efficacious agent in pancreatic cancer. A review of the experience with the Cremaphor formulation hinted at paclitaxel's activity in pancreatic cancer, but the early development was hampered by significant toxicities such as neutropenia and infection at clinically tolerable doses. However, such efficacy was confirmed in the recently completed phase III Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), in which the addition of nab-paclitaxel to gemcitabine significantly improved the survival of patients with metastatic pancreatic cancer. Several other Cremaphor-free formulations of paclitaxel had also been evaluated in pancreatic cancer, and the reasons for the success of the albumin nanoparticulate are examined here. In the era of biologic and molecularly targeted agents, the success of nab-paclitaxel in recalcitrant pancreatic cancer is a timely reminder of the importance and relevance of pharmacology and novel drug delivery technology in the development of anticancer drugs.

摘要

紫杉醇在癌症治疗中有广泛的应用,但从未被认为是胰腺癌的有效药物。对 Cremaphor 制剂经验的回顾提示了紫杉醇在胰腺癌中的活性,但早期的开发受到了中性粒细胞减少症和感染等显著毒性的阻碍,而这些毒性在临床可耐受剂量下出现。然而,在最近完成的转移性胰腺腺癌临床试验(MPACT)中,这种疗效得到了证实,在该试验中,将 nab-紫杉醇与吉西他滨联合使用显著改善了转移性胰腺癌患者的生存。其他几种无 Cremaphor 制剂的紫杉醇也已在胰腺癌中进行了评估,这里检查了白蛋白纳米颗粒成功的原因。在生物和分子靶向药物的时代,nab-紫杉醇在难治性胰腺癌中的成功及时提醒我们,药理学和新型药物输送技术在抗癌药物开发中的重要性和相关性。

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