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

References

• Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28: 1756–1765.
   PubMed Web of Science ®Google Scholar
• Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2009;27:3994–4001.
   PubMed Web of Science ®Google Scholar
• Wierda W, O’Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 2005;23: 4070–4078.
   PubMed Web of Science ®Google Scholar
• Longo PG, Laurenti L, Gobessi S, et al. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood 2008;111:846–855.
   PubMed Web of Science ®Google Scholar
• Kondapaka SB, Singh SS, Dasmahapatra GP, et al. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol Cancer Ther 2003;2:1093–1103.
   PubMed Web of Science ®Google Scholar
• Ghobrial IM, Roccaro A, Hong F, et al. Clinical and translational studies of a phase II trial of the novel oral Akt inhibitor perifosine in relapsed or relapsed/refractory Waldenstrom's macroglobulinemia. Clin Cancer Res 2010;16:1033–1041.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Wolf J, Jakubowiak A, et al. Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial. J Clin Oncol 2011;29:4243–4249.
   PubMed Web of Science ®Google Scholar
• Hassanein NM, Perkinson KR, Alcancia F, et al. A single tube, four-color flow cytometry assay for evaluation of ZAP-70 and CD38 expression in chronic lymphocytic leukemia. Am J Clin Pathol 2010; 133:708–717.
   PubMed Web of Science ®Google Scholar
• Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446–5456.
   PubMed Web of Science ®Google Scholar
• Weinberg JB, Volkheimer AD, Chen Y, et al. Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia. Am J Hematol 2007;82:1063–1070.
   PubMed Web of Science ®Google Scholar
• Levesque MC, Ghosh DK, Beasley BE, et al. CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant. Leuk Res 2008;32: 1061–100.
   PubMed Web of Science ®Google Scholar
• Woo EW, Messmann R, Sausville EA, et al. Quantitative determination of perifosine, a novel alkylphosphocholine anticancer agent, in human plasma by reversed-phase liquid chromatography-electrospray mass spectrometry. J Chromatogr B Biomed Sci Appl 2001;759:247–257.
   PubMed Web of Science ®Google Scholar
• Mowery YM, Weinberg JB, Kennedy MN, et al. LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells. Leukemia 2010;24:1580–1587.
   PubMed Web of Science ®Google Scholar
• Therneau T. A package for survival analysis in S. R package version 2.36-14 [Internet]. 2012. Available from: http://CRAN.R-project.org/package = survival
   Google Scholar
• Ritz C, Streibig JC. Bioassay analysis using R. J Stat Software 2005;12:1–22.
   Web of Science ®Google Scholar
• Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343:1910–1916.
   PubMed Web of Science ®Google Scholar
• Furman RR, Byrd JC, Brown JR, et al. CAL-101, An isoform-selective inhibitor of phosphatidylinositol 3-kinase P110{delta}, demonstrates clinical activity and pharmacodynamic effects in patients with relapsed or refractory chronic lymphocytic leukemia. Blood 2010;116(Suppl. 1): Abstract 55.
   Google Scholar
• Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3’-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011;118:3603–3612.
   PubMed Web of Science ®Google Scholar
• Crul M, Rosing H, de Klerk GJ, et al. Phase I and pharmacological study of daily oral administration of perifosine (D-21266) in patients with advanced solid tumours. Eur J Cancer 2002;38:1615–1621.
   PubMed Web of Science ®Google Scholar
• Vlahos CJ, Matter WF, Hui KY, et al. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 1994;269:5241–5248.
   PubMed Web of Science ®Google Scholar
• Van Ummersen L, Binger K, Volkman J, et al. A phase I trial of perifosine (NSC 639966) on a loading dose/maintenance dose schedule in patients with advanced cancer. Clin Cancer Res 2004;10: 7450–7456.
   PubMed Web of Science ®Google Scholar
• Bendell JC, Nemunaitis J, Vukelja SJ, et al. Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer. J Clin Oncol 2011;29:4394–4400.
   PubMed Web of Science ®Google Scholar
• van der Luit AH, Vink SR, Klarenbeek JB, et al. A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol Cancer Ther 2007; 6:2337–2345.
   PubMed Web of Science ®Google Scholar
• Gajate C, Mollinedo F. Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Blood 2007; 109:711–719.
   PubMed Web of Science ®Google Scholar
• Fu L, Kim YA, Wang X, et al. Perifosine inhibits mammalian target of rapamycin signaling through facilitating degradation of major components in the mTOR axis and induces autophagy. Cancer Res 2009;69:8967–8976.
   PubMed Web of Science ®Google Scholar
• David E, Sinha R, Chen J, et al. Perifosine synergistically enhances TRAIL-induced myeloma cell apoptosis via up-regulation of death receptors. Clin Cancer Res 2008;14:5090–5098.
   PubMed Web of Science ®Google Scholar
• Perl AE, Kasner MT, Shank D, et al. Single-cell pharmacodynamic monitoring of s6 ribosomal protein phosphorylation in AML blasts during a clinical trial combining the mTOR inhibitor sirolimus and intensive chemotherapy. Clin Cancer Res 2012;18:1716–1725.
   PubMed Web of Science ®Google Scholar