Are all gonadotrophin‐releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review

Abstract

To review direct comparative studies of the gonadotrophin-releasing hormone (GnRH) agonists goserelin, triptorelin, and leuprorelin for the treatment of prostate cancer, and identify whether there are meaningful clinical differences between these agents. In June 2017, the following searches were performed independently by two reviewers in PubMed: (i) 'prostate cancer' and 'triptorelin' and 'leuprorelin', (ii) 'prostate cancer' and 'triptorelin' and 'goserelin', and (iii) 'prostate cancer' and 'goserelin' and 'leuprorelin', without time restriction. Duplicates were deleted. Relevant conference abstracts were also screened. A total of 16 direct comparative trials were identified: 12 reported on efficacy outcomes, four on safety/tolerability, and five on the convenience of administration/user perceptions. These studies are restricted in terms of patient numbers, formulations assessed, and endpoints measured; none were adequately powered for survival outcome measures. Studies reporting on efficacy endpoints did not show major differences in the ability of these GnRH agonists to reduce levels of testosterone or prostate-specific antigen. Some studies suggest differences in short- or long-term testosterone control, the rate of injection site adverse events, and patient/healthcare professional perceptions, but definitive conclusions cannot be drawn from the existing evidence. Few direct comparative trials of GnRH agonists have been conducted. Whilst GnRH agonists provide a similar castration effect, there is not enough evidence to show that GnRH agonists are equivalent.

Leuprorrelina versus Gosserrelina no tratamento de câncer de próstata avançado: estudo de custo minimização

“…Não houve diferenças estatisticamente significativas nos níveis de castração ao comparar leuprolida 3,75 mg, leuprolida 7,5 mg e goserelina 3,6 mg. 13 Por outro lado, um estudo de revisão conduzido em 2017 concluiu que, embora os agonistas de LHRH proporcionem um efeito de castração semelhante, não há evidências suficientes para mostrar que os medicamentos são equivalentes. 14 No protocolo brasileiro não há indicação sobre qual agonistas de LHRH deve ser escolhido para o tratamento do CaP. 8 Entretanto, apenas o AG tem evidência científica de ser utilizada adjuvante a radioterapia.…”

A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy

“…Reviews have encountered difficulties in comparing agents as they have been tested in different populations. 1 17 There is at least one study suggesting that in the setting of patients receiving radiotherapy, triptorelin was more effective than the other agents that were tested. [18] …”

Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety

“…Continuous GnRH receptor activation causes down-regulation and desensitization to reduce endogenous steroid hormone biosynthesis and release [93]. Consequently, GnRH super-agonists have been successfully employed in hormone-dependent cancers in what is termed androgen deprivation therapy (ADT) [92,94].…”