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Pharmacy World and Science

, Volume 18, Issue 5, pp 163–170 | Cite as

Etoposide phosphate, the water soluble prodrug of etoposide

  • A. H. I. Witterland
  • C. H. W. Koks
  • J. H. Beijnen
Articles

Abstract

Etoposide (Vepesid) is a widely used drug in a variety of neoplasms. To improve the pharmaceutical characteristics of etoposide, etooside phosphate (Etopophos, Bristol-Myers Squibb) has been developed as a prodrug.

Etoposide phosphate is the phosphate ester derivative of etoposide, in comparison to the parent compound, etoposide phosphate is highly soluble in water and can be readily formulated for intravencus uso resulting in higher ctinical application. This paper presents information on the pharmaceutical properties and the current status of etoposide phosphate in clinical triafs.

Keywords

Alkaline phosphatase Etoposide Etoposide phosphate Mechanism of action Pharmaceutical formulation Pharmacokinetics Prodrug 

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References

  1. 1.
    StähelinHF, vonWartburgA. The chemical and biological route from podophyllotoxin glucoside to etoposide: Ninth Cain Memorial Award Lecture. Cancer Res 1991;51:5–15.Google Scholar
  2. 2.
    O'DwyerPJ, Leyland-JonesB, AlonsoMT, MarsoniS, WittesRE. Drug therapy. Etoposide (VP-16-213). Current status of an active anticancer drug. N Engl J Med 1985;312:692–700.Google Scholar
  3. 3.
    HenwoodJM, BrogdenRN. Etoposide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in combination chemotherapy of cancer. Drugs 1990;39(3):438–90.Google Scholar
  4. 4.
    BeijnenJH, Beijnen-BandhoeAU, DubbelmanAC, VanGijnR, UnderbergWJM. Chemical and physical stability of etoposide and teniposide in commonly used infusion fluids. Parenteral Science & Technology 1991;45:108–12.Google Scholar
  5. 5.
    Investigator brochure: BMY-40481 Etoposide phosphate. Wallingiord, CT, Bristo-Myers Squibb 1991.Google Scholar
  6. 6.
    BeijnenJH, HolthuisJJM, KerkdijkHG, van derHouwenOAGJ, PaelmanACA, BultA. Degradation kinetics of etoposide in aqueous solution Int J Pharm 1988; 41:169–78.Google Scholar
  7. 7.
    WebsterLK, CrinisNA, DavisJR, MillwardMJ. Conversion of etoposide phosphate to etoposide under ambulatory intusion Condition. J Oncol Pharm Practic 1995; 1: 33–6.Google Scholar
  8. 8.
    SepterPD, SaulnierMG, SchreiberGJ, HirschbergDL BrownJP, HellströmKE. Anti-tumor effects of antibody-alkaline phosphatese conjugates in combination with etoposide phosphate. Proc Natl Acad Sci USA 1988;85:4842–6.Google Scholar
  9. 9.
    RoseWC, BaslerGA, TrailPA, SaulnierM, CrosswellAR, CasazzaAM. Preclinical antitumor activity of a soluble etoposide analog, BMY-40481-30. Invest New Drugs 1990 8:S25-S32.Google Scholar
  10. 10.
    SchacterLP, LgwemezieLN, SeyedsadrM, MorgenthienE, RandolphJ, AlbertE. Clinical and pharmacolinetic overview of parenteral etoposide phosphate. Cancer Chemother Pharmacol 1994;34 (suppl):S58-S63.Google Scholar
  11. 11.
    HarrisH. The human alkaline phosphatases: wnat we know and what we don't know. Clin Chim Acta 1989;186:133–50.Google Scholar
  12. 12.
    SievinML, ClarkPL, JoelSP, MalikS, OsborneRJ, GregoryWM. Arandomized trial to evaluate the effect of schedule on the acitivity of etoposide in small-cell lung cancer. J Clin Oncol 1989;7(9):1333–40.Google Scholar
  13. 13.
    ClarkPJ, SlevinML, JoelSP, OsborneRJ, TalbotDI, JohnsonPWM. A rancomized trial of two etoposide schedules in small-cell lung cancer: the influence of pharmacokinetics on efficacy and toxicity. J Clin Oncol 1994;12(7):1427–35.Google Scholar
  14. 14.
    GrecoFA. Future directions for etoposide therapy. Cancer 1991;67(suppl):315–18.Google Scholar
  15. 15.
    SlevinML, JoelSP, WhomsleyR, DevenportK, HarveyVJ, OsborneRJ. the effect of dose on the bioavailability of oral etoposide: confirmation of a clinically relevant observation. Cancer Chemother Pharmacol 1989;24:329–331.Google Scholar
  16. 16.
    WailsThM, LohnsonDH, HainsworthJD, HandeKR, ThomasM, GrecoA. Prolonged administration of oral etoposide in non-small-cell lung cancer: a phase II trial. J Clin Oncol 1992;10:292–6.Google Scholar
  17. 17.
    HandeKR, KrozelyMG, GrecoFA, HainswortJD, JohnsonDH. Bioavailability of low-dose oral etoposide. J Clin Oncol 1993;11:374–7.Google Scholar
  18. 18.
    ThompsonDS, HainsworthJD, HandeKR, HolzmerMC, GrecoFA. Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study. J Clin Oncol 1993;11:1322–8.Google Scholar
  19. 19.
    MinamiH, ShimokataK, SakaH, SaitoH, AndoY, SendaK. Phase I clinical and pharmacokinetic study of a 14-day infusion of etoposide in patients with lung cancer. J Clin Oncol 1993;11:1602–8.Google Scholar
  20. 20.
    SchwinghammerTL, ReillyM. Cracking of ABS plastic devices usd to infuse undiluted etoposide injection. Am J Hosp Pharm 1988;45:1277.Google Scholar
  21. 21.
    Hoetelmans, RMW, Schornagel, JH, ten Bokkel Huinink WW, Beijnen JH. Hypersensitivity reactions to etoposide. Ann Pharmacother 1996; 30367–71.Google Scholar
  22. 22.
    HudsonMM, WeinsteinHJ, DonaldsonSS, GreenwaldC, KunL, TarbellNJ. Acute hypersensitivity reactions to etoposide in a VEPA regimen for Hodgkin'S disease. J Clin Oncol 1993;11:1080–4.Google Scholar
  23. 23.
    KöhlP, KöpplerH. SchmidtL, FritschHW, HölzJ, PflügerKH. Pharmacokinetics of high-dose etoposide after short-term infusion. Cancer Chemother Pharmacol 1992;29:316–20.Google Scholar
  24. 24.
    ChaoNJ, SteinAS, LongGD, NegrinRS, AmylonMD, WongRM. Busulfan/etoposide-initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukrmia. Biood 1993;81:319–23.Google Scholar
  25. 25.
    Gaastvan derA, SonneveldP, MansDRA, SplinterTAW. Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data. Cancer Chemother Pharmacol 1992;29:335–7.Google Scholar
  26. 26.
    KiyaK, UozumiT, OgasawaraH, SugiyamaK, HottaT, MikamiT. Penetration of etoposide into human malignant brain tumors after intravenous and oral administration. Cancer Chemother Pharmacol 1992;29:339–42.Google Scholar
  27. 27.
    PostmusPE, HolthuisJJM, Haaxma-ReicheH, MulderNH, VenckenLM, OortvanWJ. Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration. J Clin Oncol 1984;2:215–20.Google Scholar
  28. 28.
    HoshinoT, KumasakaK, KawanoK, KoyamaI, Arai-FujimoriY, YamagishiF. Abnormal alkaline phosphatase of hepatic type in cerebrospinal fluid of a patient with intracranial metastasis from lung cancer. J Clin Pathol 1993;46:1059–61.Google Scholar
  29. 29.
    BalmannoK, MillwardMJ, NewallDR, CharltonCJ, GumbrellL, LindMJ. Clinical and pharmacokinetic study of BMY40481 (etoposide phosphate). Br J Cancer 1992;65(suppl. XVI):42.Google Scholar
  30. 30.
    BudmanDR, IgwemezieLN, KaulS, BehrJ, LichtmanS, SchulmanPh. Phase I evaluatin of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors. J Clin Oncol 1994;12(9):1902–9.Google Scholar
  31. 31.
    FieldsSZ, IgwemezieLN, KaulS, SchacterLP, SchilderRJ, LitamPP. Phase I study of etoposide phosphate (Etopophos) as a 30-minute infusion on days 1,3, and 5. Clin Cancer Res 1995;1:105–11.Google Scholar
  32. 32.
    ThompsonDS, CrecoFA, MillerAA, SrinvasNR, IgwemezieLN, HainsworthJD. A phase I study of etoposide phosphate administered as a daily 30-minute infusion for 5 days. Clin Pharmacol Ther 1995;57:499–507.Google Scholar
  33. 33.
    FieldsSZ, BudmanDR, KreisW, SchacterLP, WrightJ, LitamP. A phase I study of high dose etoposide phosphate (EP) 2 hour infusio days 1 and 2. Proc Am Ass Clin Oncol 1995;14:481.Google Scholar
  34. 34.
    KaulS, LinusN, IgwemezieDJ, StewartSZ, FieldsSZ, KostyM. Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors. J Clin Oncol 1995;13:2835–41.Google Scholar
  35. 35.
    MillwardMJ, NewellDR, CharltonCJ, GumbrellLA, LindMJ, Dore-GreenF. Etoposide phosphate (EP): a comparative intrapatient bio-equivalence study with etoposide (E). Eur J Cancer 1993;29A (suppl. 6):5108.Google Scholar
  36. 36.
    ShahJC, ChenJR, ChowD. Preformulation study of etoposide: II. Increased solubility and dissolution rate by solid-solid dispersions. Int J Pharm 1995;113:103–111.Google Scholar
  37. 37.
    SessaC, ZucchettiM, CernyT, PaganiO, CavalliF, DeFuscoM. Phase I clinical and pharmacokinetic study of oral etoposide phosphate. J Clin Oncol 1995;13:200–9.Google Scholar
  38. 38.
    HainsworthJD, LevitanN, WamplerGI, BelaniChP, SeyedsadrMS, RandolphJ. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol 1995;13:1436–42.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • A. H. I. Witterland
    • 3
  • C. H. W. Koks
    • 3
  • J. H. Beijnen
    • 1
    • 2
  1. 1.Dept. of Medical OncologyAntoni van Leetwenhoek Hospital/The netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Dept. of Pharmaceutical Analysis & ToxicologyFaculty of PharmacyUtrechtThe Netherlands
  3. 3.Dept. of PharmacySlotervaart Hospital/Netherlands Cancer InstituteAmsterdamThe Netherlands

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