Updated Licence For Goserelin (Zoladex 3.6 Mg & Zoladex La 10.8mg) Reflects Survival Benefits In All Stages Of Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology;  Regulatory Affairs / Drug Approvals
Article Date: 08 Aug 2008 - 0:00 PDT

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The Medicines and Healthcare products Regulatory Agency (MHRA) has approved an updated licence to goserelin 3.6mg and goserelin LA 10.8mg [i] to reflect survival benefits in all three stages of prostate cancer (localised, locally advanced and advanced also called metastatic).

AstraZeneca welcomes this licence update, which distinguishes goserelin from the other LHRHas (luteinising-hormone-releasing-hormone agonist) as the only LHRHa with demonstrated survival benefits in all stages of prostate cancer.

A European trial of 415 men with high-risk localised or locally advanced prostate cancer shows that a quarter of more men will live longer at five years when goserelin is added to radiotherapy compared to radiotherapy alone. [ii] In locally advanced disease, one of the longest and largest studies of its kind (n= 977), demonstrated that when added to radiotherapy as compared to treatment with radiotherapy alone [iii], goserelin provided men with clinical benefits increasing their chance of survival by a quarter and also showed that 60% more men remain free from disease recurrence. Additionally, for prostate cancer patients where the cancer has not spread to other parts of the body yet, goserelin has been shown to consistently control prostate cancer allowing many men with locally advanced prostate cancer to out-live their disease. [iv]

In advanced cancer, goserelin demonstrates comparable survival and improved quality of life compared to surgical castration (removal of the testes also called orchidectomy). [v]

Commenting on the licence update Dr Heather Payne, Consultant Clinical Oncologist in Urological Tumours, University College Hospital, London stated: Prostate cancer is a complicated disease and can be treated in several different ways. Depending on the stage of the cancer, a clear understanding of the supporting clinical evidence for treatments should guide prescribing decisions. As healthcare professionals, we need to provide patients with the most appropriate evidence-based treatment and care at all times."

AstraZeneca firmly supports the licence update and believes this will allow clinicians to choose the most appropriate hormonal treatment to improve patients' survival.

Goserelin (Zoladex®) is a trademark of the AstraZeneca group of companies.

Goserelin (Zoladex®)

- Goserelin is a Luteinizing Hormone-Releasing Hormone agonist (LHRHa) which works in prostate cancer by reducing the levels of testosterone in men stopping prostate cancer growth. This is called 'medical castration' as opposed to a surgical castration (orchidectomy), the removal of the testes.

- Goserelin is given as an injectable implant LHRHa either every 28 days or every 12 weeks, which is implanted into the abdominal wall via subcutaneous injection by nurses or doctors.

Licence amendment

The amended wording of the goserelin 3.6mg and LA 10.8mg indication, in sections 4.1 and 5.1 of the Zoladex SmPC, is:

4.1 Therapeutic indications

Zoladex is indicated (see also section 5.1):

- In the treatment of metastatic prostate cancer where Zoladex has demonstrated comparable survival benefits to surgical castrations

- In the treatment of locally advanced prostate cancer, as an alternative to surgical castration where Zoladex has demonstrated comparable survival benefits to an anti-androgen

- As adjuvant treatment to radiotherapy in patients with high-risk localised or locally advanced prostate cancer where Zoladex has demonstrated improved disease-free survival and overall survival

- As neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced prostate cancer where Zoladex has demonstrated improved disease-free survival

- As adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression where Zoladex has demonstrated improved disease-free survival

5.1 Pharmacodynamic Properties

Zoladex (D-Ser(But)6Azgly10 LHRH) is a synthetic analogue of naturally occurring luteinising-hormone releasing hormone (LHRH). On chronic administration Zoladex LA results in inhibition of pituitary luteinising hormone secretion leading to a fall in serum testosterone concentrations in males. Initially, Zoladex LA like other LHRH agonists transiently increases serum testosterone concentrations.

In men by around 21 days after the first depot injection, testosterone concentrations have fallen to within the castrate range and remain suppressed with treatment every 12 weeks.

In the management of patients with metastatic prostate cancer, Zoladex has been shown in comparative clinical trials to give similar survival outcomes to those obtained with surgical castrations.

In a combined analysis of 2 randomised controlled trials comparing bicalutamide 150 mg monotherapy versus castration (predominantly in the form of Zoladex), there was no significant difference in overall survival between bicalutamide-treated patients and castration-treated patients (hazard ratio = 1.05 [CI 0.81 to 1.36]) with locally advanced prostate cancer. However, equivalence of the two treatments could not be concluded statistically.

In comparative trials, Zoladex has been shown to improve disease-free survival and overall survival when used as an adjuvant therapy to radiotherapy in patients with high risk localised (T₁-T₂ and PSA of at least 10 ng/mL or a Gleason score of at least 7), or locally advanced (T₃-T₄) prostate cancer. The optimum duration of adjuvant therapy has not been established; a comparative trial has shown that 3 years of adjuvant Zoladex gives significant survival improvement compared with radiotherapy alone. Neo-adjuvant Zoladex prior to radiotherapy has been shown to improve disease-free survival in patients with high risk localised or locally advanced prostate cancer.

After prostatectomy, in patients found to have extra-prostatic tumour spread, adjuvant Zoladex may improve disease-free survival periods, but there is no significant survival improvement unless patients have evidence of nodal involvement at time of surgery. Patients with pathologically staged locally advanced disease should have additional risk factors such as PSA of at least 10 ng/mL or a Gleason score of at least 7 before adjuvant Zoladex should be considered. There is no evidence of improved clinical outcomes with use of neo-adjuvant Zoladex before radical prostatectomy.

References

[i] Goserelin (Zoladex) 3.6mg and LA 10.8mg SPC http://emc.medicines.org.uk/

[ii] Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360(9327):103-108

[iii] Pilepich MV, Winter K, Lawton CA et al. Androgen suppression adjuvant to definitive radiotherapy in carcinoma of the prostate - Long term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 2005; 61(5) 1285-1290

[iv] Fleshner N, Keane TE, Lawton CA et al. Adjuvant androgen deprivation therapy augments cure and long-term cancer control in men with poor prognosis, nonmetastatic prostate cancer. Prostate Cancer Prostatic Dis 2007; 1-7

[v] Kaisary AV, Tyrrell CJ, Peeling WB et al Br.J.Urol. 1991; 67: 502-508

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