Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies. Issue 5 (May 2014)

• Record Type: Journal Article
• Authors: Friedman, Daphne R.; Lanasa, Mark C.; Davis, Patricia H.; Allgood, Sallie D.; Matta, Karen M.; Brander, Danielle M.; Chen, Youwei; Davis, Evan D.; Volkheimer, Alicia D.; Moore, Joseph O.; Gockerman, Jon P.; Sportelli, Peter; Weinberg, J. Brice
• Is Part Of: Leukemia & lymphoma. Volume 55:Issue 5(2014:May)
• Page Start: 1067
• Page End: 1075
• Publication Date: 2014-05
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.824080
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated <italic>in vitro</italic> cytotoxicity induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the mean 50% effective dose (ED₅₀) was 313 nM. We then performed a phase II trial of perifosine in patients with relapsed/refractory CLL to assess response, outcomes, toxicity and <italic>ex vivo</italic> correlative measures. After 3 months of treatment, six of eight patients showed stable disease, one achieved a partial response and one had progressive disease. Median event-free survival and overall survival in all patients treated were 3.9 and 9.7 months. Adverse events included hematologic, infectious/fever, pain, gastrointestinal and constitutional toxicities. Unexpectedly, AKT phosphorylation in CLL lymphocytes from treated patients was not correlated with response. Additionally, perifosine did not inhibit AKT phosphorylation in cultured CLL lymphocytes. Perifosine is cytotoxic to CLL cells <italic>in vitro</italic>, and largely induces stabilized disease <italic>in vivo</italic>, with an AKT-independent mechanism.</p> </abstract>