Perifosine (KRX-0401) is a novel oral bioavailable phospholipid originally under development by KERYX Biopharmaceuticals. Phospholipids have displayed significant antiproliferative activity in several human tumor types through inhibition of the Akt protein. Akt appears to be activated by most anti-cancer therapies conferring cell survival and proliferation. The anti-Akt action of perifosine may enhance the effects of other treatment agents by promoting apoptosis and interfering with cell growth signals. It also appears to induce apoptosis through JNK activation.
A phase II trial of Perifosine plus imatinib mesylate (Gleevec) is being carried out at several locations for patients whose GIST has progressed on imatinib treatment. This trial is ongoing but is no longer recruiting new patients. For further trial information link to NCT00455559. The trial is sponsored jointly by AOI Pharma and MD Anderson Cancer Center.
A Phase I trial of perifosine plus sorafenib is ongoing but no longer recruiting. For details click here.
A phase I trial of perifisone plus sunitinib (Sutent) was done but has closed. For details link here.
Link here for manufacturer information about this drug.
One paper published about a Phase II trial of perifosine in sarcoma patients did observe some prolonged responses (Bailey et al, 2006) with gastrointestinal toxicity and fatigue being the main adverse events.
For medical papers pertaining to this drug (not with respect to GIST) link to this PubMed search.