Perifosine in renal cell carcinoma.

INTRODUCTION

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.

AREAS COVERED

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.

EXPERT OPINION

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.