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)

Leuprorelin acetate, a highly potent gonadotrophin-releasing hormone agonist, was originally launched in the USA as a daily injection for the treatment of metastatic prostatic cancer. A once-monthly injectable depot form was subsequently developed. Biodegradable copoly(DL-lactic/glycolic) acid was chosen as the release-controlling polymer, and microspheres containing leuprorelin acetate were prepared by the in-water drying method. Results of studies in rats showed that a copolymer with a molecular weight of 14,000 and a lactic/glycolic acid ratio of 75/25 had the most satisfactory release-controlling properties. Microspheres given once monthly reduced serum testosterone levels in male rats. Microspheres also reduced serum oestradiol levels and caused a marked regression in experimental endometriosis in female rats. In clinical studies of prostatic cancer, use of the depot formulation has effectively reduced the dose required to as low as one-eighth of that needed for administration by daily injection. A sophisticated manufacturing system has now been developed and products now available have many advantages.
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PMID:Formulation study of leuprorelin acetate to improve clinical performance. 160 92

In a preliminary multicentre clinical trial of 3.75 mg leuprorelin acetate depot 18 previously untreated patients with metastatic prostatic cancer were treated with the depot given subcutaneously once every 4 weeks for 28 weeks. Patients also received 100 mg nilutamide taken orally three times a day for the first 14 days of treatment to prevent flare-up. Leuprorelin acetate suppressed the serum testosterone concentration to castration levels; luteinizing hormone levels were also suppressed. The incidence of progressive disease was low and partial response occurred in five patients after treatment. No side-effects were assigned to the flare-up period. It is concluded that leuprorelin acetate depot is a safe and efficacious treatment for metastatic prostatic cancer.
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PMID:Preliminary clinical evaluation of leuprorelin acetate depot injection in France, in the management of prostatic cancer. 210 87

A total of 40 patients with stages A2 to C prostatic cancer were treated with leuprorelin acetate depot once a month for 2 months before being treated by pelvic irradiation or radical prostatectomy. In the 32 patients who were evaluable, seven (22%) were classified as minor responders after leuprorelin treatment and 23 (72%) as major responders when assessed by rectal examination. Prostate-specific antigens also returned to normal concentrations (5 ng/ml) in 26/31 (84%) patients. Leuprorelin acetate depot suppressed plasma testosterone concentrations to castration values during treatment, but concentrations returned to normal 2 months after completion of treatment. Following radical treatment, there were three deaths--one postoperative and two due to recurrent disease--but there was no isolated local relapse. It is concluded that the protocol was locally well tolerated and was effective in the treatment of stages B2 and C prostatic cancer patients.
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PMID:Clinical experience with leuprorelin acetate before radiotherapy for prostatic cancer. 210 88

The clinical efficacy and safety of 3.75 or 7.5 mg leuprorelin acetate depot given subcutaneously once every 4 weeks was evaluated in a collaborative study of 81 patients with untreated prostatic cancer. Efficacy of treatment was assessed using criteria based on a meeting of the Prostatic Cancer Study Group funded by the Japanese Ministry of Health and Welfare and using National Prostatic Cancer Project criteria. Japanese criteria enabled evaluation of individual parameters, unlike the National Prostatic Cancer Project system which classified a patient as unevaluable if one evaluation parameter was unavailable. Leuprorelin acetate depot suppressed serum luteinizing hormone, follicle stimulating hormone and testosterone concentrations. Objective response rates of the prostate, bone metastases, serum prostatic acid phosphatase and soft tissue metastases, and subjective dysuria and pain responses were comparable to those found with conventional hormone therapy. Leuprorelin acetate depot was well tolerated, with no significant differences in response to the two doses.
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PMID:Leuprorelin acetate depot: results of a multicentre Japanese trial. TAP-144-SR Study Group. 210 89

Leuprorelin acetate, a highly potent luteinizing hormone releasing hormone agonist, was originally launched in the USA to be administered once daily by self-injection for the treatment of metastatic prostatic cancer. A once-monthly intramuscularly or subcutaneously injectable depot form of leuprorelin acetate has, subsequently, been developed. Biodegradable copoly(DL-lactic acid/glycolic acid) was chosen as the release-controlling polymer and the microcapsules containing leuprorelin acetate were prepared by an in-water drying method. Results of studies in rats showed that a copolymer with a molecular weight of 14,000 and a lactic acid/glycolic acid ratio of 75/25 had the most satisfactory releasing properties. Microcapsules given once monthly reduced serum testosterone levels in rats, dogs and man. In clinical studies, the depot preparation effectively reduced the dose of leuprorelin acetate required to up to one-eighth of that needed when injected daily. A sophisticated manufacturing system has now been developed and a very reliable controlled-release product is now available that has many advantages.
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PMID:Pharmaceutical manipulation of leuprorelin acetate to improve clinical performance. 213 86

In a series of studies of the immunobiological sequelae of oestrogens, the in-vitro effect of diethystilboestrol (DES) and the luteinizing-hormone-releasing-hormone leuprolide (Lupron) on the lytic activity of natural killer (NK) cells have been evaluated. Ficoll-Hypaque gradient-isolated human peripheral blood mononuclear cells (PBMC) were pre-incubated with varying concentrations of DES and leuprolide and the degree of lysis for the human erythroleukemia K-562 cell line was evaluated in a 51Cr-release assay. PBMC pre-incubated with DES exhibited an 82% reduction in the ability of NK cells to lyse K-562 target cells compared with a negligible 3% increase with leuprolide (p less than 0.001) vs. untreated PBMC. The inhibitory effects of DES or leuprolide were not due to cytotoxicity since the viability of PBMC incubated for 18 and 24 h (corresponding to the DES/leuprolide preincubation time and the NK cell assay, respectively) was comparable to that of untreated (control) cells. These observations demonstrate the further suppressive effects of DES on components of immunosurveillance. Pending evaluation of the effect of leuprolide on the activity of NK cells for other target cells, and other parameters of immunologic responsiveness, leuprolide may prove to be a favorable alternative to DES, both in view of its reduced clinical side-effects, and because of the suggested absence of deleterious effects to the immune system. Maintenance of tumour-host equilibrium, and some degree of immunocompetency, in the presence of effective therapy with leuprolide, may prove beneficial in achieving more effective therapy in prostate cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro effects of diethylstilboestrol and the LHRH analogue leuprolide on natural killer cell activity. 245 86

Leuprolide acetate is a highly potent analog of luteinizing hormone-releasing hormone. We have prepared 1-month release injectable microcapsules of leuprolide acetate using a biodegradable polymer, poly (dl-lactide-co-glycolide), to treat an endocrine-dependent tumor, prostate cancer. In the present study, the possibility using the microcapsules to treat endometriosis was investigated. In rats, the microcapsules exhibited a pseudo-zero order release from the injection site for 1 month after being administered s.c. and i.m., and maintained effective constant serum levels of the analog during the 4-week treatment. A single injection of the microcapsules (100 micrograms/kg/day as leuprolide acetate) suppressed luteinizing hormone, follicle-stimulating hormone and estradiol for more than 4 weeks, and caused a dramatic regression of growth of Jones experimental endometriosis model in female rats. These results encourage the belief that a 1-month release parenteral preparation of leuprolide acetate may be potentially useful in the therapy of endometriosis in human beings.
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PMID:One-month release injectable microcapsules of a luteinizing hormone-releasing hormone agonist (leuprolide acetate) for treating experimental endometriosis in rats. 312 94

Recent studies suggest even low dosages of oestrogen currently used for treatment of prostate cancer increase cardiovascular morbidity. In addition, relapse following growth of hormone - insensitive cells, and the present observations of further evidence of immunosuppression demonstrated by the significant (p less than 0.001) effect of DES on the lytic activity of natural killer cells vs. the negligible effect of the luteinizing - hormone - releasing - hormone, leuprolide (Lupron) raises concern that the palliative effects of oestrogen therapy are possibly further compromised by a reduction in immunosurveillance to tumour, or equally important, by a decreased capacity to cope with infectious agents.
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PMID:Leuprolide vs. diethylstilboestrol: effect on natural killer cells. 312 59

Leuprolide (Lupron, TAP Pharmaceuticals), a potent agonist analogue of GnRH, has been shown to suppress testicular androgen production in animals. In order to determine the potential of leuprolide as an alternative to surgical castration in human males with prostatic cancer, this agent was administered to castrate and noncastrate males with carcinoma of the prostate. Baseline and treatment levels of LH, FSH, testosterone and dihydrotestosterone were determined serially. Leuprolide suppressed pituitary production of LH and FSH and, consequently, testicular production of testosterone and dihydrotestosterone. This agent simulates the results achieved with surgical castration.
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PMID:Evaluation of synthetic agonist analogue of gonadotropin-releasing hormone (leuprolide) on testicular androgen production in patients with carcinoma of prostate. 391 77

A prospective evaluation of neoadjuvant hormonal downsizing in patients with localized carcinoma of the prostate was undertaken to assess its effect on normal tissue irradiation. Twenty patients with stage T1 or T2 (A, B) carcinoma of the prostate received 3 months of Lupron prior to definitive radiotherapy. The volumes of the prostate, seminal vesicles, bladder, and rectum from both the pre- and posthormone treatment planning CT were entered onto a 3-D treatment-planning system. The treatment planning parameters were standardized to facilitate comparison of the pre- and posthormonal volumes. Following the three monthly injections of Lupron, the average volume of the prostate was reduced by 37%. As a consequence, the volume of the bladder receiving at least 40, 52, and 64 Gy was reduced by an average of 15, 18, and 20%, respectively. In addition, the volume of the rectum receiving at least 40, 52, and 64 Gy was reduced by an average of 13, 20, and 34%, respectively. In conclusion, in patients with localized prostate cancer, downsizing of the prostate resulted in a reduction in the volume of bladder and rectum receiving high radiation doses. This approach may result in an improvement in the therapeutic ratio by reducing the morbidity of treatment.
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PMID:Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation. 941 69


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