The use of the LHRH-analogue Buserelin in the treatment of prostatic cancer. A 10-year review on 1522 patients treated in 119 centres on 4 continents.

In the ten years from 1979-1988, a total of 1725 patients with advanced prostatic cancer were entered into 28 studies, in which Buserelin as a nasal spray was the main androgen deprivation therapy. Patients treated with orchiectomy or other anti-androgen agents used in comparative groups, were considered unsuitable for the purpose of this study, which pools the data of the 1522 patients who received Buserelin monotherapy. Patients with stages C, D1 or D2 prostatic cancer who received Buserelin as monotherapy and had a known treatment duration were eligible for efficacy analysis. The clinical evaluation was done in 91% by NPCP-criteria and in the remainder by criteria of the EORTC or ECOG. Seventy-five per cent of the patients received Buserelin nasal spray (3x daily 400 mcg), 20% received subcutaneous injections (2x daily 200 mcg) and 4% received 2 combinations of nasal spray, subcutaneous injections and depot, or depot alone. Compliance failures were found in 4.4% and 2.4% stopped treatment due to adverse reactions. Statistical analysis includes Kaplan-Meier estimates of time-to-progression and survival. Since 1985, after 2 patients died from possible fare reactions, anti-androgens have been recommended as additional therapy for the first few weeks. Features of this analysis of great interest are the national differences in progression-free survival and overall survival.

Sustained suppression of testosterone production by the luteinising-hormone releasing-hormone agonist buserelin in patients with advanced prostate carcinoma. A new therapeutic approach?

Nine patients with advanced carcinoma of the prostate were treated with the luteinising-hormone-releasing-hormone agonist buserelin (2 mg/day subcutaneously for 3 days then 0.4-1.2 mg/day intranasally for up to 24 weeks). There was a rise in luteinising-hormone levels during the first few days of treatment, but levels fell after 3 weeks and remained lower than normal after 24 weeks' treatment. In patients receiving 0.6-1.2 mg buserelin per day testosterone levels fell to less than 1 ng/ml within 3 weeks and were still as low as those found in surgically castrated men after 24 weeks. Histology showed regressive changes in some tumours after 3-6 months' buserelin treatment similar to those seen in surgically castrated men. Buserelin treatment may be an alternative to surgery in patients with advanced carcinoma of the prostate.

Endocrine studies with a gonadotropin-releasing hormone analogue to achieve withdrawal of testosterone in prostate carcinoma patients.

This investigation on 12 well-defined patients with untreated, advanced prostatic adenocarcinoma establishes the gonadotropin-releasing hormone analogue [D-Ser(But)6](1-9)-nonapeptide-ethylamide (Hoe 766) as an effective, safe and non-toxic form of medical castration. Hoe 766 was given either as subcutaneous injections of 2 x 200 micrograms/day over 14 days and pernasal application (3 x 400 micrograms/day) thereafter, or as subcutaneous injections of 3 x 1,000 micrograms/day over 6 days and pernasal application thereafter in the dosage mentioned above. Both dose regimens were equally effective: pituitary overstimulation between days 3 and 6 with a rise of serum HL and testosterone; pituitary and testicular desensitization with LH and testosterone decline between days 6 and 14; medical castration with average serum testosterone levels maintained around 0.5 ng/ml for up to 12 weeks. Except for transient hot flashes in 4 patients, no clinical or laboratory side effects were observed. It is concluded from this study that the gonadotropin-releasing hormone analogue. Hoe 766, is a valuable alternative to conventional contrasexual measures for prostate cancer palliation. To improve the patient's compliance, however, the smallest single pernasal dosage effective for maintenance of down-regulation and steroidogenic arrest has still to be determined.