Treatment of Advanced Prostatic Cancer with Buserelin, an Analogue of Gonadotrophin Releasing Hormone

Abstract

Twenty-two consecutive patients with newly diagnosed symptomatic, locally advanced or metastatic prostate cancer were treated with intranasal buserelin, a long-acting analogue of gonadotrophin releasing hormone, in divided dosages of between 600 and 1000 micrograms daily. Suppression of testosterone occurred in 1 of 5 patients treated with 600 micrograms daily and in all 17 patients receiving 1000 micrograms daily. Two of 5 patients treated with the 600 micrograms regimen and 16 of 17 patients receiving the 1000 micrograms regimen showed subjective and objective evidence of disease regression. Follow-up was from 1 to 16 months (mean 7.1 months); 6 patients have relapsed during this period. Buserelin offers an effective alternative medical treatment of carcinoma of the prostate and, apart from impotence, does not have the side effects of oestrogens.

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

“…Furthermore, biomacromolecules such as peptides and proteins are marketed for hormone replacement therapies. For instance, nasal sprays containing salmon calcitonin (Miacalcin®, Novartis; Fortical®, Unigene) are available on the market to treat osteoporosis; desmopressin (Desmospray®, Ferring) is used IN as a antidiuretic hormone to treat diabetes insipidus, enuresis, haemophilia A and the von Willenbrand's disease (type I), and gonadotropin-releasing hormone analogs such as busrelin (Suprecur®, Sanofi-Aventis) and nafarelin (Synarel®, Pharmacia) are used to reduce the testosterone and oestrogen levels in blood of patients suffering of prostate cancer and endometriosis [105,[135][136][137][138][139][140]. None of these products contain any absorption enhancers, even though systemic bioavailability of peptides and proteins after IN application is usually below 1%.…”

Active cell death in hormone-dependent tissues

“…These include anti-androgens which interfere with the steroid receptor mechanism [4][5][6]; compounds, such as ketoconazole and finasteride, which interfere with steroid metabolism [7][8][9][10][11]; and combination therapy using anti-androgens in combination with GnRH analogues, anti-prolactins [12][13][14][15][16][17][18] or aminoglutethimide [19]. Despite continued refinement in hormonal therapies, there has been a distressing lack of improvement in the disease-free interval or the overall five-year survival rate of patients with prostatic carcinoma [1,[20][21][22][23][24].…”