Beth Israel Deaconess Medical Center, Division of Hematology and Oncology, 330 Brookline Avenue, MASCO 4th Floor, Boston, MA 02215, USA.
Expert Opin Investig Drugs. 2013 Feb;22(2):285-91. doi: 10.1517/13543784.2013.754422. Epub 2012 Dec 20.
Perifosine is an oral alkylphospholipid which has recently been assessed clinically in patients with advanced renal cell carcinoma (RCC). Perifosine acts primarily by attenuating the activation of Akt by preventing its pleckstrin homology (PH) domain-dependent localization to the cell membrane.
This review summarizes the therapeutic landscape of RCC including the proposed role of perifosine in patients with advanced RCC. The mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy in RCC and safety of perifosine are all addressed as well.
Although perifosine has clear clinical activity in RCC, it is not superior to currently available agents and therefore does not appear worthy of further clinical development in RCC as a single agent. Given the observed efficacy and mild toxicity, however, perifosine may have a role in RCC therapy given in combination with other molecularly targeted agents.
帕非索辛是一种口服烷基磷酯，最近已在晚期肾细胞癌（RCC）患者中进行了临床评估。帕非索辛主要通过阻止其pleckstrin 同源（PH）结构域依赖性定位于细胞膜，从而减弱 Akt 的激活。
本文综述了 RCC 的治疗现状，包括帕非索辛在晚期 RCC 患者中的作用。还讨论了帕非索辛的作用机制、药效学、药代动力学、在 RCC 中的临床疗效和安全性。
尽管帕非索辛在 RCC 中具有明确的临床活性，但它并不优于目前可用的药物，因此作为单一药物，似乎不值得进一步在 RCC 中进行临床开发。然而，鉴于观察到的疗效和轻微的毒性，帕非索辛可能在与其他分子靶向药物联合治疗 RCC 中具有作用。
