Clinical effects of gonadotropin-releasing hormone analogue in metastatic carcinoma of prostate

Smith, Joseph A.; Glode, L. Michael; Wettlaufer, J. S.; Stein, Barry S.; Glass, Andrew G.; Max, D. T.; Anbar, Dan; Jagst, Cheryl; Murphy, Gerald P.

doi:10.1016/0090-4295(85)90523-0

Cited by 77 publications

(17 citation statements)

References 14 publications

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“…Men who received leuprorelin after previous hormonal manipulation showed only minimal evidence of response with 5% having partial response, 43% having disease stabilization, and 52% having disease progression [20].…”

Section: Cook Sheridan 165mentioning

confidence: 99%

“…Approximately 88% of patients achieved disease stabilization, although complete responses were rare. No significant differences between the responses to 1 or 10 mg/day were noted [20,23] or to 3.75 or 7.5 mg depot each month [27,29,30]. The median response duration was between 10 and 18 months, and the median survival was about two years.…”

Section: Cook Sheridan 165mentioning

confidence: 99%

“…Several noncomparative studies of leuprorelin (leuprolide acetate) administered as a daily injection or monthly depot injection have been reported [20][21][22][23][24][25][26][27][28][29][30][31]. Patients enrolled in these clinical trials had previously untreated histologically confirmed metastatic or locally advanced disease.…”

Section: Agonistsmentioning

confidence: 99%

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Development of GnRH Antagonists for Prostate Cancer: New Approaches to Treatment

2000

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Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer‐related death. Several treatment options exist for different stages of prostate cancer including observation, prostatectomy, radiation therapy, chemotherapy, and hormone therapy. Hormone therapy has evolved from the use of estrogens to gonadotropin‐releasing hormone (GnRH) agonists and recently, investigational GnRH antagonists. GnRH receptor agonists such as leuprolide, bruserelin and goserelin have been used for the treatment of prostate cancer. These agonists eventually cause the inhibition of lutenizing hormone production, which in turn causes a suppression of testosterone and dihydrotestosterone, on which continued growth of prostate cancer cells depend. Several comparative studies of leuprorelin administered as daily injections or monthly depot injections have been reported. Disease progression was prevented in more than 72% of men administered daily leuprorelin, and in 82% to 89% of those receiving monthly depots. Another synthetic GnRH analog, goserelin, has been studied in a similar population of men with daily injections producing partial responses in 60% to 80% of men with previously untreated prostate cancer. Abarelix, a peptide antagonist of GnRH receptor, is also being studied for the treatment of prostate cancer. The discovery and development of GnRH antagonists may provide an important advance for patients with prostate cancer. Clearly the studies described herein, as well as many others, outline an exciting era of research to define the optimal use of hormonal therapy in prostate cancer.

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Section: Cook Sheridan 165mentioning

confidence: 99%

Section: Cook Sheridan 165mentioning

confidence: 99%

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Development of GnRH Antagonists for Prostate Cancer: New Approaches to Treatment

2000

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“…All patients were oestrogen receptor positive or unknown. Serum (Jacobi et al, 1987;Smith et al, 1985; Donnelly & Milstead, 1987) and breast cancer (Harvey et al, 1985;Klijn, 1984;Williams et al, 1986). This is due to the 'down-regulation' of LHRH receptors by the drugs, which results in a fall in gonadotrophin levels and a consequent reduction in the level of gonadal steroid production (Sandow, 1983).…”

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confidence: 99%

A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients

Dowsett

Mehta²,

Mansi³

et al. 1990

Br J Cancer

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Summary Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum (Jacobi et al., 1987;Smith et al., 1985; Donnelly & Milstead, 1987) and breast cancer (Harvey et al., 1985;Klijn, 1984;Williams et al., 1986). This is due to the 'down-regulation' of LHRH receptors by the drugs, which results in a fall in gonadotrophin levels and a consequent reduction in the level of gonadal steroid production (Sandow, 1983). The response rate is higher in premenopausal patients in breast cancer as might be expected for a drug with this action. The small number of responses in postmenopausal patients may be due to reduced ovarian androgen secretion with a consequent fall in circulating oestrogen levels (Dowsett et al., 1988;Crighton et al., 1989).Leuprorelin is a synthetic nonapeptide LHRHa (D-Leu6 DES Gly NH2iO GnRH ethylamide) which lacks the aminoacid glycine at position 10 and has leucine substituted for glycine at position 6 of natural LHRH. Earlier clinical studies required daily administration in aqueous solution (Harvey et al., 1985), but a more convenient sustained release formulation has now been developed, in which the agonist is microencapsulated in polylactic and polyglycolic acid. It has been found that the compound is equally effective endocrinologically in prostatic cancer as once monthly doses of either 7.5 or 3.75 mg (Isurugi et al., 1988). This is the first report of the use of the slow-release formulation in premenopausal women. A detailed endocrine study was conducted to compare the doses of 3.75 and 7.5 mg in 12 patients, to determine whether there was any contraindication to further study of the lower dose in a larger group of patients. Blood samples were drawn from patients prior to treatment and 1, 2, 3, 4, 6, 8, 10 and 12 weeks after starting treatment. The samples were allowed to clot and the resultant serum was stored at -20°C until analysis. The following analyses were performed by previously described immunoassays: luteinising hormone (LH) and follicle stimulating hormone (FSH) (Ferguson et al., 1982); oestradiol (Dowsett et al., 1987), oestrone (Harris et al., 1983). Serum levels of androstenedione were measured using the Biogenesis kit. This is a direct assay employing an iodinated tracer in which the only cross-reactions of greater than 0.1 % were to 11-deoxycortisol (1.2%) and isoandrosterone (0.3%). Withinand between-assay coefficients of variation were 7.5% and 8.6%, respectively. Serum levels of testosterone were measured using the St Thomas Hospital Testosterone kit (Wheeler et al., 1983). In this assay, the serum is first extracted with ether and this extract is subject to immunoassay using an iodinated tracer. The antiserum cross-reacts 20% with 5adihydrotestosterone. All other cross-reactions were less than 0.1%. Within-and between-assay coefficients of variation were ...

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“…Although a number of authors have reported on the effect of hormone therapy in advanced prostate cancer, few reports are available on the therapeutic effect of applying this treatment regimen to localized or locally advanced prostate cancer (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Early Results of LH-RH Agonist Treatment with or without Chlormadinone Acetate for Hormone Therapy of Naive Localized or Locally Advanced Prostate Cancer: A Prospective and Randomized Study

Akaza

Homma²,

Okada³

et al. 2000

Japanese Journal of Clinical Oncology

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Background:The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. Methods: A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostatespecific antigen level, progression-free survival and survival were observed for 2 years. Results: The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p < 0.05). Group II showed a longer progression-free survival (p < 0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. Conclusions: Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

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Clinical effects of gonadotropin-releasing hormone analogue in metastatic carcinoma of prostate

Cited by 77 publications

References 14 publications

Development of GnRH Antagonists for Prostate Cancer: New Approaches to Treatment

Development of GnRH Antagonists for Prostate Cancer: New Approaches to Treatment

A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients

Early Results of LH-RH Agonist Treatment with or without Chlormadinone Acetate for Hormone Therapy of Naive Localized or Locally Advanced Prostate Cancer: A Prospective and Randomized Study

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