Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies.

Published

Journal Article

Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro 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 ex vivo 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 in vitro, and largely induces stabilized disease in vivo, with an AKT-independent mechanism.

Full Text

Duke Authors

Cited Authors

  • Friedman, DR; Lanasa, MC; Davis, PH; Allgood, SD; Matta, KM; Brander, DM; Chen, Y; Davis, ED; Volkheimer, AD; Moore, JO; Gockerman, JP; Sportelli, P; Weinberg, JB

Published Date

  • May 2014

Published In

Volume / Issue

  • 55 / 5

Start / End Page

  • 1067 - 1075

PubMed ID

  • 23863122

Pubmed Central ID

  • 23863122

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

International Standard Serial Number (ISSN)

  • 1042-8194

Digital Object Identifier (DOI)

  • 10.3109/10428194.2013.824080

Language

  • eng