Drugs

, Volume 70, Issue 3, pp 347–353 | Cite as

Triptorelin Embonate (6-Month Formulation)

Adis Drug Profile

Abstract

A 6-month formulation of the gonadotropin-releasing hormone agonist triptorelin embonate (designed to deliver 22.5 mg of triptorelin over a 6-month period) has been developed for use in the treatment of advanced prostate cancer.

Following intramuscular administration of the 6-month formulation of triptorelin embonate 22.5 mg to men with advanced prostate cancer (subset of 15 patients from the pivotal clinical trial), serum testosterone levels initially increased, followed by a rapid, sustained decrease. Castrate serum testosterone levels (i.e. ≤1.735nmol/L) wereachieved in a geometric mean time of 18.8 days.

The 6-month formulation of triptorelin embonate achieved and maintained castrate serum testosterone levels in patients with advanced prostate cancer (n= 120), according to the results of the pivotal, non-comparative, multicentre trial (patients received intramuscular triptorelin embonate 22.5 mg on day 1 and at month 6 [week 24]). By day 29, 97.5% of patients had castrate serum testosterone levels. Castrate serum testosterone levels were maintained from months 2 to 12 in 93.0% of patients. Prior to the second injection at month 6, 98.3% of patients had castrate serum testosterone levels, and 98.3% of patients had castrate serum testosterone levels at study completion.

The 6-month formulation of triptorelin embonate 22.5 mg was generally well tolerated in patients with advanced prostate cancer; adverse events were of mild severity in the majority of patients. Drug-related adverse events (e.g. hot flushes) were consistent with the pharmacological action of triptorelin. Injection-site reactions occurred in 6.7% of triptorelin embonate recipients.

Notes

Acknowledgements and Disclosures

The manuscript was reviewed by: C.F. Heyns, Departement Urologie, Universiteit Stellenbosch en Tygerberg-hospitaal, Tygerberg, South Africa; H. Isbarn, University Hospital Hamburg-Eppendorf, Department of Urology, Hamburg, Germany.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

References

  1. 1.
    Ferlay J, Autier P, Boniol M. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007 Mar; 18(3): 581–92CrossRefPubMedGoogle Scholar
  2. 2.
    Horwich A, Parker C, Kataja V. Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008; 19 Suppl. 2: 45–6Google Scholar
  3. 3.
    Miller K, Anderson J, Abrahamsson P-A. Treatment of prostate cancer with hormonal therapy in Europe. BJU Int 2009 Mar; 103 Suppl. 2: 2–6CrossRefGoogle Scholar
  4. 4.
    National Institute for Health and Clinical Excellence. Prostate cancer: diagnosis and treatment [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/CG58FullGuideline.pdf [Accessed 2009 Dec 8]
  5. 5.
    Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol 2008 Jan; 53(1): 68–80CrossRefPubMedGoogle Scholar
  6. 6.
    Anderson J, Abrahamsson P-A, Crawford D, et al. Management of advanced prostate cancer: can we improve on androgen deprivation therapy? BJU Int 2008 Jun; 101(12): 1497–501CrossRefPubMedGoogle Scholar
  7. 7.
    Heyns CF. Triptorelin in the treatment of prostate cancer: clinical efficacy and tolerability. Am J Cancer 2005; 4(3): 169–83CrossRefGoogle Scholar
  8. 8.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology™: prostate cancer v.2.2009 [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf [Accessed 2009 Dec 9]
  9. 9.
    Coy DH, Vilchez-Martinez JA, Coy EJ, et al. Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6. J Med Chem 1976; 19: 423–5CrossRefPubMedGoogle Scholar
  10. 10.
    Lundström EA, Rencken RK, van Wyk JH, et al. Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study. Clin Drug Invest 2009; 29(12): 757–65CrossRefGoogle Scholar
  11. 11.
    Botto H, Roupret M, Mathieu F, et al. Multicentre randomized trial comparing triptorelin medical castration versus surgical castration in the treatment of locally advanced or metastatic prostate cancer [in French]. Prog Urol 2007 Apr; 17(2): 235–9CrossRefPubMedGoogle Scholar
  12. 12.
    Bolla M, De Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009 Jun 11; 360(24): 2516–27CrossRefPubMedGoogle Scholar
  13. 13.
    Ipsen. Ipsen’s Decapeptyl® 6-month formulation receives marketing authorization in France for the treatment of locally advanced or metastatic prostate cancer [media release]. Available from URL: http://www.ipsen.com/articles/mediacentre/pressreleases/20091113___amm_decapeptyl_france_10.pdf [Accessed 2009 Dec 10]
  14. 14.
    Ipsen. Ipsen and Debiopharm Group announce that Decapeptyl® (triptorelin embonate) 6-month successfully completes the European decentralised procedure for the treatment of locally advanced or metastatic prostate cancer [media release; online]. Available from URL: http://www.ipsen.com/articles/mediacentre/pressreleases/20091013___decapeptyl_6_months_10.pdf [Accessed 2009 Dec 10]
  15. 15.
    European Medicines Agency. Triptorelin 22.5 mg: summary of product characteristics. 2009Google Scholar
  16. 16.
    Barron JL, Millar RP, Searle D. Metabolic clearance and plasma half-disappearance time of D-TRP6 and exogenous luteinizing hormone-releasing hormone. J Clin Endocrinol Metab 1982 Jun; 54(6): 1169–73CrossRefPubMedGoogle Scholar
  17. 17.
    Redding TW, Schally AV, Tice TR, et al. Long-acting delivery systems for peptides: inhibition of rat prostate tumors by controlled release of [D-Trp6] luteinizing hormone-releasing hormone from injectable microcapsules. Proc Natl Acad Sci U S A 1984 Sep; 81(18): 5845–8CrossRefPubMedGoogle Scholar
  18. 18.
    Redding TW, Schally AV. Inhibition of prostate tumor growth in two rat models by chronic administration of D-Trp6 analogue of luteinizing hormone-releasing hormone. Proc Natl Acad Sci U S A 1981 Oct; 78(10): 6509–12CrossRefPubMedGoogle Scholar
  19. 19.
    Müller FO, Terblanche` J, Schall R, et al. Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency. Br J Clin Pharmacol 1997 Oct; 44(4): 335–41CrossRefPubMedGoogle Scholar
  20. 20.
    Debiopharm S.A. Clinical study report: a multicentre, open, non-comparative, phase III study on the efficacy, pharmacokinetics and safety of two injections of triptorelin embonate 22.5 mg 6-month formulation in patients with advanced prostate cancer. Debiopharm S.A., 2008 May. (Data on file)Google Scholar

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© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore 0754, AucklandNew Zealand

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