European Journal of Cancer
Volume 46, Issue 5 , Pages 920-925 , March 2010

First-time-in-man and pharmacokinetic study of weekly oral perifosine in patients with solid tumours

  • Clemens Unger

      Affiliations

    • Klinik für Tumorbiologie an der Albert-Ludwigs Universität, Freiburg, Germany
    • Corresponding Author InformationCorresponding author: Address: Klinik für Tumorbiologie an der Albert-Ludwigs Universität Freiburg, Breisacher Str. 117, D-79106 Freiburg, Germany. Tel.: +49 761 206 1801; fax: +49 761 206 1199.
    • ,
  • Wolfgang Berdel

      Affiliations

    • Med. Klinik A der Universität Münster, Innere Medizin, Hämatologie, Internistische Onkologie und Pulmologie, Münster, Germany
    • Present address.
    • ,
  • Axel-R Hanauske

      Affiliations

    • AK St.Georg, Hamburg, Germany
    • Present address.
    • ,
  • Herbert Sindermann

      Affiliations

    • Aeterna Zentaris GmbH, Frankfurt am Main, Germany
    • ,
  • Jürgen Engel

      Affiliations

    • Aeterna Zentaris GmbH, Frankfurt am Main, Germany
    • ,
  • Klaus Mross

      Affiliations

    • Klinik für Tumorbiologie an der Albert-Ludwigs Universität, Freiburg, Germany

Received 29 September 2009 ,Revised 15 December 2009 ,Accepted 18 December 2009.

References 

  1. Unger C, Sindermann H, Peukert M, et al. Hexadecylphosphocholine in the topical treatment of skin metastases in breast cancer patients. Prog Exp Tumor Res. 1992;34:153–159
  2. Sundar S, Jha TK, Thakur CP, et al. Oral miltefosine for Indian visceral leishmaniasis. New Engl J Med. 2002;347:1739–1746
  3. Danhauser-Riedl S, Drozd A, Zafferani M, et al. Phase I study with weekly oral miltefosine (hexadecyl-phosphocholine) in cancer patients. Onkologie. 1991;14:392–400
  4. Verweij J, Planting A, van der Burg M, Stoter G. A dose-finding study of miltefosine (hexadecylphosphocholine) in patients with metastatic solid tumours. J Cancer Res Clin Oncol. 1992;118:606–608
  5. Hilgard P, Klenner T, Stekar J, Nössner G, Kutscher B, Engel J. D-21266, a new heterocyclic alkylphospholipid with antitumor activity. Eur J Cancer. 1997;33:442–446
  6. Vink SR, Lagerwerf S, Mesman E, et al. Radiosensitization of squamous cell carcinoma by the alkylphospolipid perifosine in cell culture and xenografts. Clin Cancer Res. 2006;12:1612–1622
  7. Ruiter GA, Zerp SF, Bartelink H, van Blitterswijk WJ, Verheij M. Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway. Anticancer Drugs. 2003;14:167–173
  8. Ruiter GA, Zerp SF, Bartelink H, van Blitterswijk WJ, Verheij M. Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer Res. 1999;59:2457–2463
  9. Ruiter GA, Verheij M, Zerp SF, Moolenaar WH, Van Blitterswijk WJ. Submicromolar doses of alkyl-lysophospholipids induce rapid internalization, but not activation, of epidermal growth factor receptor and concomitant MAPK/ERK activation in A431 cells. Int J Cancer. 2002;102:343–350
  10. Kondapaka SB, Singh SS, Dasmahapatra GP, Sausville EA, Roy KK. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol Cancer Ther 2003;11:1093–1103.
  11. Hideshima T, Catley L, Raje N, et al. Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells. Brit J Haematol. 2007;138:783–791
  12. Knebel NG, Grieb S, Winkler M, et al. Quantification of perifosine, an alkylphosphocholine anti-tumour agent, in plasma by pneumatically assisted electrospray tandem mass spectrometry coupled with high-performance liquid chromatography. J Chromatogr B: Biomed Sci Appl. 1999;721:257–269
  13. Crul M, Rosing H, de Klerk GJ, et al. Phase I and pharmacological study daily oral administration of perifosine (D-21266) in patients with advanced solid tumours. Eur J Cancer. 2002;38:1615–1621
  14. Van Ummersen L, Binger K, Volkmann 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
  15. Pronk LC, Planting ASTh, van Oosterom A, et al. Increases in leucocyte and platelet counts induced by the alkyl phospholipid hexadecylphosphocholine. Eur J Cancer. 1994;30A:1019–1022
  16. Vink S, Schellens JHM, Beijnen JH, et al. Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumors. Radiother Oncol. 2006;80:207–213
  17. Bailey HH, Mahoney MR, Ettinger DS, et al. Phase II study of oral perifosine in patients with advanced soft tissue sarcoma. Cancer. 2006;107:2462–2467
  18. Ghobrial IM, Leleu X, Rubin N, et al. Phase II trial of the novel oral Akt inhibitor perifosine in relapsed and/or refractory Waldenstrom macroglobulinemia (WM). ASCO Meeting Abstracts (J Clin Oncol) 2008;26:8546.

PII: S0959-8049(09)00959-9

doi: 10.1016/j.ejca.2009.12.028

European Journal of Cancer
Volume 46, Issue 5 , Pages 920-925 , March 2010

Article Tools

* Image Usage & Resolution