goserelin and abarelix

In the 60 years since Huggins first demonstrated the hormone dependency of prostate cancer, the introduction of various means of hormonal manipulation has resulted in modest achievements. Orchiectomy reduced testosterone but was irreversible and associated with reduced quality of life. Diethylstilbestrol (DES) represented the first alternative to surgical castration. However, cardiovascular adverse events severely limited its use. The luteinizing hormone-releasing hormone (LHRH) agonists offered true medical castration but suffered from problems of testosterone surge and tumor flare. The introduction of antiandrogens in combination with LHRH agonists appears on meta-analysis not to have improved survival and has implications for the cost and convenience of therapy, as well as added toxicity. Gonadotropin-releasing hormone (GnRH) antagonists offer for the first time a truly rapid medical means of reducing testosterone and also suppress follicle-stimulating hormone (FSH). However, the clinical benefit of this new class of drugs remains to be evaluated.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oligopeptides; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Study Type - Therapy (prospective cohort). Level of Evidence 2a. What's known on the subject? and What does the study add? The sequential administration of a GnRH antagonist followed by an LHRH agonist in the management of prostate cancer patients has not been studied, but such a program would provide a more physiologic method of achieving testosterone suppression and avoid the obligatory testosterone surge and need for concomitant antiandrogens that accompany LHRH agonist therapy. The current study which uses abarelix initiation therapy for 12 weeks followed by either leuprolide or goserelin demonstrates the ability to more rapidly achieve testosterone suppression, avoid the obligatory LHRH induced testosterone surge, avoid the necessity of antiandrogens, all of which were accomplished safely, without inducing either additional or novel safety issues.. • To demonstrate the safety and endocrinological and biochemical efficacy of initiating treatment with the gonadotropin-releasing hormone (GnRH) antagonist, abarelix, followed by administration of an luteinizing hormone-releasing hormone (LHRH) agonist in patients with advanced and metastatic prostate cancer.. • A multicentre, open-label design study was conducted at 22 centres in the US involving patients with: localized, locally advanced or metastatic disease; with a rising prostate-specific antigen (PSA) after definitive local treatment; patients undergoing neoadjuvant hormonal therapy before local therapy (radical prostatectomy, radiation therapy or cryosurgery); and patients in whom intermittent therapy was the planned treatment. • All patients received abarelix for 12 weeks followed by an LHRH agonist (either leuprolide or goserelin) for 8 weeks • The primary efficacy endpoint was achievement and maintenance of castration defined as testosterone <50 ng/dL from day 29 through to day 141 and whether abarelix initiation therapy could eliminate the testosterone surge after two consecutive doses of LHRH agonist therapy. • PSA, LH and follicle-stimulating hormone (FSH) levels were measured and adverse events were monitored.. • A total of 176 patients were enrolled into the present study, the majority of whom had localized prostate cancer (82%) and a PSA level <10 ng/mL (62%). • At the end of the abarelix treatment period (day 85), 93.8% of patients achieved castrate levels; during the first week of switch over to the LHRH agonist therapy (days 85-92) the rate was 86.5% and during the week after the second LHRH agonist injection (days 114-12) it was 93.3%. • A small, transient increase in testosterone occurred during the first injection of the LHRH agonist; mean (standard deviation [sd]) values increased from 17 (17.8) ng/dL at day 85 to 37.3 (51.07) ng/dL at day 86. • Mean (sd) PSA levels decreased from 20.5 (56.6) ng/mL at baseline to 3.7 (23.5) ng/mL on day 85 and remained stable throughout the LHRH agonist treatment phase. • Treatment-related adverse events occurred in 84% of patients overall; a similar incidence was reported during the two treatment phases.. • Abarelix initiation therapy results in the desired effect of achieving rapid testosterone suppression; testosterone surges after subsequent LHRH agonist therapy are greatly abrogated or completely eliminated. • This treatment paradigm (abarelix initiation followed by agonist maintenance) obviates the need for an antiandrogen. • Abarelix was well tolerated and no clinically meaningful or novel adverse events were observed during abarelix treatment or in the transition to LHRH agonist maintenance therapy.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Goserelin; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; United States

We contrasted the endocrinological and biochemical efficacies of abarelix depot, a pure gonadotropin-releasing hormone antagonist, with a prospective concurrent control cohort receiving luteinizing hormone releasing hormone (LH-RH) agonists with or without antiandrogen for treatment of patients with prostate cancer receiving initial hormonal therapy.. In this phase 2 open label study 242 patients with prostate cancer requiring initial hormonal treatment received abarelix depot (209) or LH-RH agonists (33) with or without antiandrogen. A total of 100 mg. abarelix depot was delivered intramuscularly every 28 days with an additional injection on day 15. LH-RH agonists with or without antiandrogen were administered according to the depot formulation used. Endocrine efficacy was measured by the absence of testosterone surge and rapidity of castration onset. The rate of prostate specific antigen decrease was assessed.. No patient treated with abarelix depot had testosterone surge during week 1 compared with 82% of those treated with LH-RH agonists. The concomitant administration of antiandrogen had no effect. During the first week of drug administration, in 75% of patients treated with abarelix depot and in 0% of those treated with LH-RH agonist medical castration was achieved. Prostate specific antigen decrease was faster, with no flare or surge in patients treated with abarelix depot. Abarelix depot was well tolerated.. Abarelix depot represents a new class of hormonal therapy, gonadotropin releasing hormone antagonists, that has rapid medical castration and avoids the testosterone surge characteristic of LH-RH agonists.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Dihydrotestosterone; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intramuscular; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testis; Testosterone