Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in January 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

In 2013, the licensed indications for the luteinising hormone-releasing hormone (LHRH) agonist, triptorelin (Decapeptyl SR), were extended to include 2 new indications for prostate cancer: neoadjuvant treatment before radiotherapy in high-risk localised or locally advanced disease, and adjuvant treatment to radical prostatectomy in locally advanced disease at high risk of progression. These are based on limited clinical data on the use of triptorelin and extrapolation from evidence for other LHRH agonists.

Effectiveness

  • In 2 single-arm randomised controlled trials (n=28 and n=50), compared with baseline, neoadjuvant triptorelin for 2 or 3 months before radiotherapy statistically significantly reduced prostate volume (p<0.001). In 1 study (n=50) it also reduced prostate-specific antigen levels (p<0.001).

  • There are no clinical studies of triptorelin as adjuvant treatment to radical prostatectomy.

Safety

  • An initial increase in testosterone levels can cause transient worsening of signs and symptoms of prostate cancer in the first weeks.

  • LHRH agonists may reduce bone mineral density, increase the risk of depression and cause metabolic changes (glucose intolerance and increased risk of cardiovascular disease).

Patient factors

  • Intramuscular injection every 4 weeks, 3 months or 6 months.

  • An almost complete suppression of testosterone levels can cause hot flushes, erectile dysfunction and decreased libido.

Resource implications

  • Decapeptyl SR costs £69.00 for the 3 mg formulation (given every 4 weeks), £207.00 for the 11.25 mg formulation (given every 3 months) and £414.00 for the 22.5 mg formulation (given every 6 months).

Key points

Triptorelin is an LHRH (also called gonadotropin-releasing hormone [GnRH]) agonist licensed for use in prostate cancer. In May 2013, the indications for the Decapeptyl SR brand of triptorelin (3 mg, 11.25 mg and 22.5 mg formulations) were extended to include:

  • neoadjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced prostate cancer, and

  • adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression.

The licence application for neoadjuvant treatment before radiotherapy in patients with high-risk localised or locally advanced prostate cancer was supported by clinical data from 8 studies. Two of these were prospective single-arm studies of triptorelin that investigated change in prostate volume (Samper et al. 2006 and Ozyigit et al. 2003). The other 6 studies were randomised controlled trials of other LHRH agonists, mainly goserelin, which showed benefits in terms of disease progression or survival. The use of LHRH agonists as neoadjuvant treatment before radiotherapy is supported by the NICE clinical guideline on the diagnosis and treatment of prostate cancer, which was updated in January 2014. However, there are no long-term, patient-oriented outcome studies of triptorelin in this population.

Clinical data from 7 studies were submitted in support of the licence application for adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression. None of these trials used triptorelin. Goserelin was used in some trials, but androgen deprivation therapy with anti-androgens or orchidectomy was also used. The UKPAR document states that there is a lack of data to support the benefit of LHRH agonists in this population. The NICE guideline on the diagnosis and treatment of prostate cancer does not recommend adjuvant hormonal therapy in addition to radical prostatectomy, even to men with margin-positive disease, other than in the context of a clinical trial. However, goserelin (Zoladex) and leuprorelin (Prostap) are licensed for adjuvant use to radical prostatectomy, and the licensed indications for triptorelin (Decapeptyl SR) were extended to be consistent with these.

Local decision makers will need to consider the evidence for triptorelin alongside that for other LHRH agonists. Individual patient factors, and the licensed indications, dosage intervals and costs of the various LHRH agonists available will need to be taken into account in the context of NICE guidance.

Key evidence

Samper PM, López Carrizosa C, Pérez Casas A et al. (2006) Impact of neoadjuvant hormonal therapy on dose-volume histograms in patients with localized prostate cancer under radical radiation therapy. Clinical and Translational Oncology 8: 599–605

Ozyigit G, Akyol F, Onal C et al. (2003) Combined hormonotherapy and definitive radiation therapy in localized prostate adenocarcinoma. International Journal of Hematology and Oncology 13: 177–89 [translated]

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.