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

Publication ,  Journal Article
Friedman, DR; Lanasa, MC; Davis, PH; Allgood, SD; Matta, KM; Brander, DM; Chen, Y; Davis, ED; Volkheimer, AD; Moore, JO; Gockerman, JP ...
Published in: Leuk Lymphoma
May 2014

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.

Duke Scholars

Published In

Leuk Lymphoma

DOI

EISSN

1029-2403

Publication Date

May 2014

Volume

55

Issue

5

Start / End Page

1067 / 1075

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Phosphorylcholine
  • Phosphorylation
  • Neoplasm Staging
  • Middle Aged
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology
 

Citation

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MLA
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Friedman, D. R., Lanasa, M. C., Davis, P. H., Allgood, S. D., Matta, K. M., Brander, D. M., … Weinberg, J. B. (2014). Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies. Leuk Lymphoma, 55(5), 1067–1075. https://doi.org/10.3109/10428194.2013.824080
Friedman, Daphne R., Mark C. Lanasa, Patricia H. Davis, Sallie D. Allgood, Karen M. Matta, Danielle M. Brander, Youwei Chen, et al. “Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies.Leuk Lymphoma 55, no. 5 (May 2014): 1067–75. https://doi.org/10.3109/10428194.2013.824080.
Friedman DR, Lanasa MC, Davis PH, Allgood SD, Matta KM, Brander DM, et al. Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies. Leuk Lymphoma. 2014 May;55(5):1067–75.
Friedman, Daphne R., et al. “Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies.Leuk Lymphoma, vol. 55, no. 5, May 2014, pp. 1067–75. Pubmed, doi:10.3109/10428194.2013.824080.
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. Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies. Leuk Lymphoma. 2014 May;55(5):1067–1075.

Published In

Leuk Lymphoma

DOI

EISSN

1029-2403

Publication Date

May 2014

Volume

55

Issue

5

Start / End Page

1067 / 1075

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Phosphorylcholine
  • Phosphorylation
  • Neoplasm Staging
  • Middle Aged
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology