Researchers from several U.S. institutions have reported a 40% overall response rate to the combination of perifosine and Velcade® (bortizomib) in patients with multiple myeloma who had been previously treated with Velcade. The details of this study were presented at the 2008 meeting of the American Society of Hematology on December 9 in San Francisco.[1]
Perifosine belongs to a new class of anti-tumor drugs that targets cell membranes and inhibits Akt activation and induces apoptosis. This agent has been tested as a single agent in patients with breast cancer, prostate cancer, head and neck cancer, and melanoma without significant clinical effects. However, at ASH 2007 a multicenter study showed a 38% response rate and a 47% disease stabilization rate in patients with relapsed or refractory myeloma following treatment with perifosine with or without dexamethasone.[2] In vitro-studies have shown that perifosine and Velcade are synergistic against myeloma cells.[3]
The current study involved the treatment of 76 patients with relapsed/refractory multiple myeloma treated with perifosine and Velcade with or without dexamethasone. All patients had received prior therapy with Velcade, and 35 were deemed refractory to Velcade. Fifty-seven patients in this study were evaluable for response. The overall response rate was 40%, with 30% having stable disease. The median time to tumor progression for all patients was 19 weeks, while the median time to tumor progression for responders had not been achieved. The overall response rate for patients deemed refractory to Velcade was 37%, and the median time to tumor progression was 23 weeks. The combination of Velcade and perifosine was described as well tolerated.
Comments: These data suggest that pirifosine may be a useful new agent for the treatment of patients with myeloma.
References:
[1] Richardson P, Wolf J, Jakubowiak et al. Phase I/II results of a multicenter trial of perisosine (KRX-0401) + bortezomib in patients with relapsed or relapsed/refractory multiple myeloma who were previously relapsed from or refractory to bortezomib. Blood. 2008;112:321, abstract number 870.
[2] Richardson P, Lonial S, Jakubowiak A, et al. Multi-center phase II study of perifosine (KRX-0401) alone and in combination with dexamethasone (dex) for patients with relapsed/refractory multiple myeloma (MM): Promising activity as conbineation therapy with manageable toxicity. Blood. 2007;110, abstract number 1164.
[3] Hideshima T, Catley L, Yasui H, et al. Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood. 2006;107:4053-4062.
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