An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists

Koch, Michaël; Steidle, Christopher P.; Brosman, Stanley A.; Centeno, Arthur S.; Gaylis, Franklin; Campion, Marilyn; Garnick, Marc B.

doi:10.1016/s0090-4295(03)00656-3

Cited by 40 publications

(14 citation statements)

References 8 publications

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“…A total of 5 patients (2%) died in each of the 240/160 and 240/80 groups, compared with 9 (4%) in the leuprolide group. These mortality rates were similar to those reported for previous studies of other ADTs in similar patient populations [9,31]. …”

Section: Safety and Tolerabilitysupporting

confidence: 90%

Degarelix: A New Approach for the Treatment of Prostate Cancer

2009

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Androgen deprivation therapy remains the mainstay of medical treatment for prostate cancer. Generally, this is achieved with medical androgen deprivation rather than orchidectomy, as most patients find the permanency and psychological effects of the latter unacceptable. Gonadotrophin-releasing hormone (GnRH) agonists are the most widely used androgen deprivation therapy, but do have some drawbacks. The most apparent is the induction of a transient surge in serum testosterone that may stimulate tumor growth, causing patients to experience new or worsening cancer symptoms. These may include increased bone pain and urinary retention, and consequently delay the therapeutic benefit of these agents. These shortcomings led to the development of the GnRH antagonists/receptor blockers. Degarelix is a novel GnRH receptor blocker that has an immediate onset of action, producing a rapid decrease in luteinizing hormone and follicle-stimulating hormone leading to fast testosterone suppression without the initial surge associated with the GnRH agonists. Administration of subcutaneous degarelix depot has been investigated in multicenter, open-label, randomized, phase II trials of up to 1 year’s duration in patients with prostate cancer. Degarelix induced rapid luteinizing hormone suppression and fast, profound and sustained suppression of serum testosterone (≤0.5 ng/ml), with additional rapid and sustained reductions in dihydrotestosterone and prostate-specific antigen. Dose-finding trials indicate that a 240 mg starting dose and an 80 or 160 mg maintenance dose is most effective for long-term testosterone suppression. In a phase III, 1-year comparator trial, degarelix produced fast testosterone suppression and prostate-specific antigen reduction ≥2 weeks before clinically relevant changes were induced by the GnRH agonist leuprolide. Degarelix was as effective as leuprolide at reducing testosterone ≤0.5 ng/ml from 1 month to study end. Degarelix was well tolerated, with uneventful toxicology and no evidence of systemic allergic reactions. This new agent represents an important pharmacological development in the hormonal treatment of prostate cancer.

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Section: Safety and Tolerabilitysupporting

confidence: 90%

Degarelix: A New Approach for the Treatment of Prostate Cancer

2009

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“…Abarelix appear to offer an effective option in the management of prostate cancer for suppressing testosterone levels and reducing PSA, although their long‐term effects on survival have yet to be determined by clinical studies. Its potential advantages are absence of flare, rapid down‐regulation and no need for combination therapy with an antiandrogen 4,6 , 7 . It is the first GnRH antagonist which is approved by the US Food and Drug Administration for patients with advanced prostate cancer who should be treated under a risk management program.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a pituitary adenoma following a gonadotropin‐releasing hormone agonist in a patient with prostate cancer

Massoud

Paparel²,

Lopez³

et al. 2006

Int J of Urology

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Gonadotropin-releasing hormone (GnRH) agonists have become the treatment of choice for locally advanced and metastatic prostate cancer. We report a case of prostate cancer in which this treatment led to severe symptoms of intracranial hypertension due to the concomitant presence of an asymptomatic functional pituitary adenoma. A 70-year-old white man was initially evaluated for a multifocal adenocarcinoma, Gleason score 6 (3 + 3) with perineural invasion suggesting an extracapsular extension. A conformational external beam radiation (74 Gy) with a concomitant GnRH agonist (leuprolide) was initiated. Almost 10 days after the administration of leuprolide the patient complained of visual disturbance, diplopia and other symptoms of intracranial hypertension. Magnetic resonance imaging (MRI) of the brain demonstrated a large sella mass lesion. To relieve the patient's symptoms, a transsphenoidal subtotal tumorectomy was necessary. The histopathological examination revealed an invasive gonadotroph pituitary adenoma. Two years later, there is no sign of progression either on his prostatic disease (prostatespecific antigen of 0.21 ng/mL) or on his pituitary disease (FSH, 4.7 UI/L, LH, 3.1 UI/L and total testosterone, 627 ng/dL) with values of the hypothalamic-pituitary axis in the normal range. We advocate that a high index of suspicion of pituitary tumor must be considered in any case of intracranial hypertension following the administration of GnRH agonist. Abarelix could have a place in such cases.

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“…Another open‐label study of abarelix in patients with advanced symptomatic prostate cancer determined the possibility of avoiding bilateral orchidectomy; endocrine, PSA outcomes, pain scores and disease response were also assessed [18]. In all, 81 patients with primarily D1 or D2 disease received abarelix 100 mg per month for 6 months.…”

Section: Efficacymentioning

confidence: 99%

“…Faster control of testosterone levels also removes the risk of tumour stimulation. Such control has been accompanied by a reduction in risk of spinal cord compression, improvements in bladder neck outlet obstruction, reduced need of catheterization and reduced bone pain [18].…”

Section: Advantages Of Abarelix Treatmentmentioning

confidence: 99%