Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical efficacy of (D-Leu6)-des Gly-NH2(10)-LH X RH ethylamide (Leuprolide) against prostatic cancer was evaluated at the end of twelve weeks of administration of a daily dose of 20 mg subcutaneous injection to 22 patients with prostatic cancer. Of these 22 patients, 19 were previously non-treated and 3 had reactivated cancer. Complete regression was obtained in all patients with stage B or C cancer. Also, in 5 out of 12 previously non-treated patients with stage D cancer, Leuprolide administration proved to be effective for controlling prostatic cancer. However, Leuprolide therapy produced only stable effects at best in 3 patients who had reactivated cancer. It has no side effect and should be recommended as a drug of first choice in the treatment of previously non-treated prostatic cancer. It can be assumed from the present studies that the efficacy of this agent against prostatic cancer is mainly the result of its inhibitory effect on hypothalamo-pituitary testicular system, i.e., a medical castration effect.
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PMID:[Clinical efficacy of (D-Leu6)-des Gly-NH2(10)-LHRH ethylamide against prostatic cancer]. 643 16

Leuprorelin (leuprolide acetate) is a gonadotrophin-releasing hormone (GnRH) analogue used to treat a wide range of sex hormone-related disorders including advanced prostatic cancer, endometriosis and precocious puberty. It acts primarily on the anterior pituitary, inducing a transient early rise in gonadotrophin release. With continued use, leuprorelin causes pituitary desensitisation and/or down-regulation, leading to suppressed circulating levels of gonadotrophins and sex hormones. Clinical trials in men with advanced prostatic cancer demonstrate that leuprorelin (usually monthly depot injections of 3.75 or 7.5 mg) is less likely to cause serious adverse cardiovascular effects than diethylstilbestrol, and has comparable efficacy to bilateral orchiectomy or other GnRH analogues. Therefore, the choice between leuprorelin and orchiectomy may be made on the basis of the patient's treatment preference, along with specific patient characteristics and cost implications. Monthly intramuscular or subcutaneous administration of depot leuprorelin 3.75 mg was superior to placebo, and comparable to oral danazol 800 mg/day or intranasal buserelin 900 micrograms/day, in achieving objective and subjective responses in women with endometriosis. Thus, leuprorelin is an effective alternative to other treatments for women with endometriosis, but the recommended duration of its use in this clinical setting is limited to 6 months because it reduces bone mineral density. In children with central precocious puberty, leuprorelin (usually monthly intramuscular or subcutaneous injections of depot leuprorelin 3.75 to 15mg) decreases mean growth velocity and signs of sexual maturation and increases predicted adult height compared with baseline measurements. Although effects on final adult height are predicted from available data and require confirmation in long term follow-up studies, the absence of effective alternatives to GnRH analogues makes leuprorelin a first-line therapy for children with this rare disease. In women with uterine leiomyomata, monthly intramuscular administration of depot leuprorelin 3.75 mg for 6 months markedly reduces uterine volume and fibroid-related symptoms, but, as with other GnRH analogues, these effects dissipate following discontinuation of the drug. As adjuvant therapy in women undergoing in vitro fertilisation or gamete intrafallopian transfer, leuprorelin (usually 0.5 to 1 mg/day subcutaneously) reduces the risk of cancelled cycles for oocyte retrieval by preventing premature luteinisation. While some studies demonstrate an improvement in intermediate end-points such as increased number of mature oocytes retrieved and embryos available for transfer, a significant effect has not been demonstrated on the rate of live births per stimulated cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Leuprorelin. A review of its pharmacology and therapeutic use in prostatic cancer, endometriosis and other sex hormone-related disorders. 753 99

The syndrome of pituitary apoplexy has been reported to occur after the administration of several different medications. We report a case in which pituitary apoplexy developed shortly after the administration of leuprolide in a patient with prostate cancer. Leuprolide is a potent gonadotrophin releasing hormone (GnRH) analogue used to suppress leuteotrophic hormone (LH) and testosterone levels in patients with metastatic prostate cancer. LH and testosterone levels actually rise in the first week after its administration before becoming suppressed. We suspect that this acute stimulating effect of leuprolide is linked to the acute onset of pituitary apoplexy in a patient with a possible gonadotrophoma.
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PMID:Pituitary apoplexy after leuprolide administration for carcinoma of the prostate. 915 52

The indolocarbazole analogue CEP-751 is a potent and selective tyrosine kinase inhibitor of the neurotrophin-specific trk receptors that has demonstrated antitumor activity in nine different models of prostate cancer growth in vivo. In the slow-growing, androgen-sensitive Dunning H prostate cancers, which express trk receptors, CEP-751 induced transient regressions independent of effects on cell cycle. Because androgen ablation is the most commonly used treatment for prostate cancer, we examined whether the combination treatment of CEP-751 with castration would lead to better antitumor efficacy than either treatment alone. For a 60-day period, H tumor-bearing rats received treatment with either castration, CEP-751 (10 mg/kg once a day s.c. for 5 days every 2 weeks), a combination of both, or vehicle. Castration caused tumor regression, followed by tumor regrowth in 4-6 weeks, whereas intermittent CEP-751 treatments resulted in tumor regressions during each treatment, which were followed by a period of regrowth between intermittent drug treatment cycles. Overall, both monotherapies significantly inhibited tumor growth compared with the vehicle-treated control group. However, the combination of castration and concomitant CEP-751 produced the most dramatic results: sigificantly greater tumor regression than either therapy alone, with no signs of regrowth. A related experiment using an orally administered CEP-751 analogue (CEP-701), as the trk inhibitor, and a gonadotrophin-releasing hormone agonist, Leuprolide, to induce androgen ablation demonstrated similar results, indicating that these effects could be generalized to other forms of androgen ablation and other trk inhibitors within this class. In addition, when CEP-701 was given sequentially to rats bearing H tumors, which were progressing in the presence of continuous androgen ablation induced by Leuprolide, regression of the androgen-independent tumors occurred. In summary, these data demonstrate that CEP-751 or CEP-701, when combined with surgically or chemically induced androgen ablation, offer better antitumor efficacy than either monotherapy and suggest that each therapy produces prostate cancer cell death through complementary mechanisms.
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PMID:Sustained in vivo regression of Dunning H rat prostate cancers treated with combinations of androgen ablation and Trk tyrosine kinase inhibitors, CEP-751 (KT-6587) or CEP-701 (KT-5555). 1034 49

Leuprorelin has demonstrated effectiveness comparable to orchiectomy and oral diethylstilboestrol for the palliation of advanced prostate cancer. Unlike orchiectomy, leuprorelin's effects are reversible; also leuprorelin is not associated with the cardiovascular or thromboembolic adverse effects of oestrogens. For these reasons, leuprorelin has been widely used as an alternative to surgical castration or to oestrogens in the treatment of metastatic prostate cancer. Sustained-release leuprorelin microsphere formulations have been developed which exhibit zero order release of active drug from the injection site, such that in the United States the 7.5 mg dosage strength is recommended to be administered once a month and the 22.5 mg dosage strength once every three months. Although most patients will have suppressed release of pituitary luteinizing hormone by the third or fourth week after the first dose of depot leuprorelin, 4-5% of treated patients have been reported to have delayed responses, taking many more weeks or months to respond. A transient biochemical hormone escape has also been reported, although worsening of clinical symptoms has not accompanied the elevation of serum testosterone levels during treatment. Usually, leuprorelin is initiated as monotherapy when patients with advanced prostate cancer become symptomatic. However, newer studies of combination therapy of luteinizing hormone releasing hormone analogs with antiandrogens suggest that early initiation of therapy, at the time of diagnosis of advanced disease, may be beneficial, particularly in a subgroup of patients with small volume disease and good performance status. Leuprorelin is also undergoing evaluation as neoadjuvant therapy prior to radical prostatectomy for localized prostate cancer. Preliminary studies suggest that neoadjuvant leuprorelin in combination with an antiandrogen may be effective in downstaging prostate tumours. Leuprorelin commonly produces several adverse effects: hot flashes, decreased libido and impotence, and tumour flare.
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PMID:Therapeutic effects of leuprorelin microspheres in prostate cancer. 1083 68

An osmotically driven implantable system was designed and characterized for the delivery of leuprolide over a year-long duration. Leuprolide has been used in the treatment of prostate cancer since the 1980s. The DUROS implant consists of a titanium alloy cylinder, measures 4 mm in diameter by 45 mm in length and holds approximately 150 microl of formulation. Stability studies indicated that leuprolide was stable, as a solution formulation in DMSO, for several years at 37 degrees C. In vitro release rate testing, at weekly intervals, showed zero-order delivery for 1 year. DUROS implants demonstrated release rates that were reproducible and similar to one another after storage at 25 degrees C for 18 months prior to testing. In vivo studies, with implants placed subcutaneously, revealed delivery rates comparable to those observed under in vitro conditions. Leuprolide stability was also comparable between in vivo and in vitro conditions. Steady leuprolide serum levels produced by the implant resulted in the desired pharmacodynamic efficacy endpoint of testosterone suppression, both in canines and in humans. The good agreement between in vivo/in vitro delivery rates was as expected for a delivery system based on the principles of osmosis.
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PMID:An in vivo/in vitro comparison with a leuprolide osmotic implant for the treatment of prostate cancer. 1145 92

The effects of the nonsteroidal antiandrogen bicalutamide (Casodex(TM)) and the luteinizing hormone releasing hormone agonist leuprolide depot (Procren Depot(TM), Lupron Depot(TM)) on serum prostate-specific antigen (PSA), acid phosphatase (ACP), and prostatic acid phosphatase (PAP) in patients with benign prostatic hyperplasia (BPH) were determined. Thirty patients with BPH were randomised to receive bicalutamide 50 mg orally once daily or a placebo for 24 weeks, followed by 24 weeks of follow-up (bicalutamide study). In another study 55 men were randomised between 3.75 mg leuprolide depot intramuscularly at every 28 days for 24 weeks or placebo injections (leuprolide study). In both studies blood sampling was performed at baseline, at week 12 at week 24 and 24 weeks after the end of therapy. Androgen suppression with bicalutamide 50 mg daily for 24 weeks resulted in a median of 56% reduction of PSA (P<0.001 when compared to placebo). Acid phosphatase and PAP did not change. Leuprolide resulted in a median of 87% reduction of serum PSA (P<0.001) and a 39% reduction of PAP (P=0.023), whereas ACP was unchanged. Both bicalutamide and leuprolide induced a pronounced decline in serum PSA in BPH patients. The studies suggest a stronger androgen suppressive effect of leuprolide than of bicalutamide, but this difference might largely be due to too low a dosage of bicalutamide. ACP and PAP were relatively insensitive to androgen suppression. Our study suggests a different degree of androgen suppression on PSA originating from benign tissue versus cancer tissue, and that the direction of this discrepancy might be different for various androgen suppressive regimens.Prostate Cancer and Prostatic Diseases (2001) 4, 173-177.
Prostate Cancer Prostatic Dis 2001
PMID:Effects of bicalutamide and leuprolide on prostate-specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP) in men with benign prostatic hyperplasia (BPH). 1249 37

Leuprorelin is a luteinizing hormone-releasing hormone analogue, licensed in the UK for the treatment of advanced prostate cancer. This review highlights the efficacy and tolerance of this agent and the benefits provided for developing patient-centred therapy and optimizing patient quality of life.
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PMID:Leuprorelin: a leading role in advanced prostate cancer therapy. 1283 32

A novel liposomal formulation was developed for the encapsulation of the oligopeptide leuprolide (GlpHisTrpSerTyr-D-LeuLeuArgProNHEt), a potent analogue of gonadotropin releasing hormone used in the treatment of advanced prostate cancer, endometriosis and precocious puberty. Leuprolide was synthesized using solid phase methodology on a {3-[(ethyl-Fmoc-amino)-methyl]-1-indol-1-yl}-acetyl AM resin and Fmoc/tBu chemistry. The new liposomal formulation, called 'liposomes in liposomes' is composed of egg phosphatidylcholine:dipalmitoylphosphatidylglycerol in a molar ratio of 98.91:1.09 (internal liposomes) and egg phosphatidylcholine:dipalmitoylphosphatidylglycerol:cholesterol in a molar ratio of 68.71:0.76:30.53 (external liposomes). It offers high encapsulation efficiency (73.8% for leuprolide); it can provide new delivery characteristics and it may have possible advantages in future applications regarding the encapsulation and delivery of bioactive peptides to target tissues. Furthermore, the physicochemical characteristics (size distribution and zeta-potential) of the liposomal formulations and the thermal effects on leuprolide in model lipidic bilayers composed of dipalmitoylphosphatidylcholine were studied using differential scanning calorimetry. Finally, the dynamic effects of leuprolide in an egg phosphatidylcholine/cholesterol system were examined using solid state 13C MAS NMR spectroscopy.
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PMID:Synthesis, liposomal formulation and thermal effects on phospholipid bilayers of leuprolide. 1594 35

Prostate cancer (PCa) growth initially depends on circulating androgens. Gonadotropin-releasing hormone (GnRH) agonists are currently used for the treatment of PCa. However, after an initial responsiveness to hormonal deprivation, PCa progresses and metastasizes. Recently, also GnRH antagonists have been used for clinical trials in patients with PCa and the results seem promising. The components of the plasminogen activator (PA) system (urokinase-type PA, uPA; PA inhibitors, PAI-1/2; uPA receptor, uPAR) have been implicated in the local degradation of the extracellular matrix (ECM) and PCa progression. The aim of this study was to test the possible effects of the treatment with an agonist (Leuprolide, GnRH-A) and an antagonist (Cetrorelix, GnRH-ANT) of GnRH on the expression and activity of uPA and PAI-1 in the conditioned media of DU145 and PC3, two PCa androgen-independent cell lines. The involvement of the PA system in the control of cellular migration was also investigated. The results obtained in DU145 and PC3 cells show that both GnRH-A and GnRH-ANT: i) inhibit cell proliferation; ii) significantly decrease the enzymatic activity and the secretion of uPA; iii) significantly increase the protein levels of PAI-1; iv) induce a significant decrease of the migratory and invasion PCa capabilities. This study suggests that GnRH analogues exhibit not only an antiproliferative effect, but also an anti-metastatic action exerted through the inhibition of the activity of PA system and might provide a rational basis for the development of clinical strategies for those tumours that progress towards an androgen-independent condition characterized by a higher metastatic potential.
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PMID:GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system. 1639 60


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