Importance of Early Tumour Exacerbation in Patients Treated With Long Acting Analogues of Gonadotropin Releasing Hormone for Advanced Prostatic Cancer

Waxman, Jonathan; Man, A.; Hendry, W. F.; Whitfield, H. N.; Besser, G. M.; Tiptaft, R. C.; Paris, A. M. I.; Oliver, R.T.D.

doi:10.1016/s0022-5347(17)45994-5

Cited by 8 publications

(11 citation statements)

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“…1B) and the serum total testosterone level was maintained below the castration threshold for 3 months (data not shown). No patients complained about flare-up-like symptoms such as pain exacerbation, dysuria, and spinal cord compression (Waxman et al, 1985) after goserelin injection. This clinical study demonstrated that sequential administration of the GnRH antagonist followed by the GnRH agonist stably decreased serum total testosterone to the castration level even after treatment with the GnRH agonist.…”

Section: Resultsmentioning

confidence: 99%

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Elucidation of the mechanism of suppressed steroidogenesis during androgen deprivation therapy of prostate cancer patients using a mouse model

et al. 2016

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SUMMARYAndrogen deprivation therapy (ADT) is the standard medical approach to the management of prostate cancer. Patients switched from a GnRH antagonist to a GnRH agonist, did not experience a testosterone surge in spite of the occurrence of luteinizing hormone (LH) surge in our protocol of clinical study. To clarify this observation, male mice pre-treated with two different doses of the GnRH antagonist degarelix for 28 days were further administered the GnRH agonist leuprolide or chorionic gonadotropin, and testosterone production of the mice was studied. Serum LH and testosterone levels, the size of Leydig cells, and expression level of steroidogenesis-related genes in the testis were analyzed. Treatment of mice with a high dose of degarelix (0.1 lg/mouse; HDG), but not a low dose (0.05 lg/mouse; LDG), for 28 days reproduced declined steroidogenesis observed in prostate cancer patients during ADT switched from a GnRH antagonist to a GnRH agonist. The size of the Leydig cells in the HDG mice was not significantly different from that in naive mice. Although expression levels of StAR, P450scc, and 17b HSD increased significantly in the LDH testis, those in the HDG testis did not change. Treatment of mice with a high dose of degarelix for 28 days reproduced the decline in steroidogenesis observed in prostate cancer patients during ADT. In this animal model, we demonstrated that initial ADT may inhibit the ability of Leydig cells to produce testosterone by suppressing the expression of genes involved in steroidogenesis, such as StAR, P450scc, and 17bHSD.

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Section: Resultsmentioning

confidence: 99%

“…Although treatment with GnRH agonists efficiently decreases serum testosterone to the castration level, it might exacerbate clinical symptoms because of a testosterone surge (Waxman et al, 1985). A long-acting GnRH agonist requires repetitive administration every 3 or 6 months (Wechsel et al, 1996;Tunn et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the mechanism of suppressed steroidogenesis during androgen deprivation therapy of prostate cancer patients using a mouse model

et al. 2016

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“…The initial physiological response to LHRH agonists results in an initial stimulation and secretion of luteinizing hormone and follicle-stimulating hormone causing a tumour flare phenomenon that may stimulate prostate cancer cells and lead to an exacerbation of clinical symptoms such as spinal cord compression, bone pain and urethral obstruction, which have been reported since the 1980s (Waxman et al, 1985). The initial physiological response to LHRH agonists results in an initial stimulation and secretion of luteinizing hormone and follicle-stimulating hormone causing a tumour flare phenomenon that may stimulate prostate cancer cells and lead to an exacerbation of clinical symptoms such as spinal cord compression, bone pain and urethral obstruction, which have been reported since the 1980s (Waxman et al, 1985).…”

Section: Androgen Deprivation Therapymentioning

confidence: 99%

‘Nurse: My back hurts!’: case study review of Degarelix in metastatic prostate cancer

Turner

Drudge-Coates

Pati

2011

International Journal of Urological Nursing

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In the management of metastatic prostate cancer, treatment with androgen deprivation therapy, initially with surgery via bilateral orchidectomy and more recently with medical therapy using gonadotropin‐releasing hormone (GnRH) agonists, has remained the key treatment approaches for this disease stage. Notably, patients express a preference towards a medical therapy approach. We present the case study of a patient with symptomatic metastatic prostate cancer treated with the new GnRH antagonist degarelix.

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“…Waxman 26 demonstrated that another possible reason for this`¯are' phenomenon could be a direct stimulation of the malignant cells that contained GnRH receptors. This sudden increase in the level of circulation androgens may cause serious side effects such as paralysis from pathological fractures due to spinal bone metastases and acute urinary retention.…”

Section: Flare Phenomenonmentioning

confidence: 99%

Combined androgen blockade for advanced prostatic carcinoma

Göktaş

Ziada

Crawford

1999

Prostate Cancer Prostatic Dis

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Hormonal therapy has been mainstay of treatment for advanced forms of prostate cancer for over 50 y. The choice of hormonal therapy for carcinoma of the prostate depends not only on the desired progression-free and overall survival but also on the patient's quality of life, treatment costs and treatment toxicities. At the present time, several important questions have been raised over optimal treatment modalities for advanced prostate cancer. The optimal form of this therapy is still an enigma.

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Importance of Early Tumour Exacerbation in Patients Treated With Long Acting Analogues of Gonadotropin Releasing Hormone for Advanced Prostatic Cancer

Cited by 8 publications

References 0 publications

Elucidation of the mechanism of suppressed steroidogenesis during androgen deprivation therapy of prostate cancer patients using a mouse model

Elucidation of the mechanism of suppressed steroidogenesis during androgen deprivation therapy of prostate cancer patients using a mouse model

‘Nurse: My back hurts!’: case study review of Degarelix in metastatic prostate cancer

Combined androgen blockade for advanced prostatic carcinoma

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