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)

This updated literature review on heterosteroids and drug research has information on chemical structure, pharmacology, and effects. It first discusses the anti-inflammatory heterosteroids, such as mometasone furoate and cortivazol. It also covers heterosteroidal antimineralocorticoids and anabolic hetero derivatives. The review discusses at length the 19-norsteroid, mifepristone (RU-486), which exhibits antiprogestational activity and is being used for fertility control in women. It also has antiglucocorticoid activity and shows promise as a treatment of diseases characterized by muscle atrophy. In vitro studies indicate that mifepristone inhibits growth of breast cancer cell lines and of endometrial cancer cell lines. It has already exhibited growth inhibitory effects in some breast cancer patients. Discussions of mifepristone's pharmacokinetics and structural modifications of mifepristone follow. Danazol is an antigonadotropin and is used to treat endometriosis, benign breast disease, precocious puberty, hereditary angioneurotic edema, menorrhagia, some types of infertility, and gynecomastia. Danazol effects considerable changes in lipid metabolism. Other hormonal, antihormonal, and/or antifertility heterosteroids and/or aspects include androgen antagonists (e.g., cyproterone acetate), estrogen activity, antiestrogens, STS-557, and oximinosteroids. Heterosteroidal inhibitors of steroid hormone biosynthesis discussed are aromatase inhibitors, 5 alpha-reductase inhibitors, and 3 beta-hydroxysteroid dehydrogenase inhibitors (trilostane, epostane, and azastene). Heterosteroids affect the cardiovascular system, including the cardiac glycosides, antiarrhythmic agents, and antilipemic agents. Some heterosteroids affect central nervous system activity (e.g., RU-5135 causes convulsions in rodents). Pancuronium analogues and chandonium and analogues are neuromuscular blocking azasteroids. In addition to danazol and RU-486, several other antineoplastic heterosteroids exist (e.g., estramustine phosphate sodium, a prostate cancer drug).
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PMID:Heterosteroids and drug research. 184 48

Little is known about the efficacy of flutamide monotherapy in previously untreated patients with prostatic carcinoma. In this study, 40 patients with advanced disease were treated with 250 mg flutamide, three times daily. The mean follow-up was 7 months. After 3 months, 35 patients were evaluable for efficacy; 17 showed a partial response and 18 showed no change. Tumor response after 6 months was evaluated in 22 patients; 10 had a partial response, nine had stable disease, and three had progression. The level of prostate-specific antigen was reduced markedly following 6 months' treatment with flutamide. Levels of testosterone increased slightly but significantly, and were still elevated not significant after a follow-up period of 1 year. Follicle-stimulating hormone did not change markedly, whereas luteinizing hormone rose significantly. Eighteen patients experienced mild gynecomastia and eight suffered diarrhea. In two patients, flutamide was discontinued for 2 weeks due to serious diarrhea. One patient was withdrawn after 6 weeks because of cholestatic hepatitis. Sexual potency was evaluated in 15 patients, 10 of whom remained sexually active during treatment. Flutamide monotherapy was concluded to be relatively safe and effective in patients with advanced prostatic cancer.
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PMID:Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. 194 17

The therapeutic efficacy and safety of various doses of leuprorelin acetate depot were determined in an open, multicentre study of patients with locally advanced or metastatic prostatic cancer (stages C, D1 or D2). Patients were randomly assigned to receive 3.75 mg (30 cases), 7.5 mg (eight cases), 15 mg (eight cases) and 30 mg (one patient) leuprorelin acetate depot administered subcutaneously once every 4 weeks. Of the 43 patients evaluable, two (5%) had complete remission, 23 (53%) partial remission and 13 (30%) patients stable disease. No significant differences were observed in response rates in relation to dose, disease stage or previous hormonal therapy. Disappearance or improvement in bone pain and urinary symptoms occurred in 63% and 79% of cases, respectively. Serum androgen concentrations decreased rapidly and persistently to castration levels, without significant differences for different doses. Treatment was well tolerated with a low incidence of mild side-effects - gynaecomastia (16%), nausea/vomiting (13%) and diarrhoea (2%). It is concluded that 3.75 mg leuprorelin acetate depot given subcutaneously once every 4 weeks is able to produce hormonal effects in all patients, an overall objective response comparable to that obtained using higher doses.
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PMID:Leuprorelin acetate depot in advanced prostatic cancer: a phase II multicentre trial. 210 83

Recently a new non-steroidal antiandrogen (Casodex) has been shown in animal experiments to possess a potent peripheral antiandrogen effect. In patients with advanced prostatic cancer however, this drug is not peripherally selectively active and blocked central brain androgen-receptors results in a rise of luteinizing hormone (LH) and testosterone (T). We treated 18 advanced prostatic cancer patients with 50 mg Casodex daily for a mean period of 42 weeks. There were no complete objective responses but partial responses were seen in a few patients. In 16 patients there was a greater than 50% reduction of pretreatment PSA levels. Endocrine evaluations showed a significant rise in LH, T and oestradiol (E), reaching peak values within the two first months with subsequent lowering of these levels afterwards but without returning to normal. The general tolerance of the drug was good, gynecomastia being the most frequent side-effect. Libido and potency, when present before start of therapy, were maintained in some patients. We conclude that this compound seems as effective as other antiandrogens, but with improved compliance, and shows less side effects in the management of advanced prostatic cancer.
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PMID:Clinical profile of a new non-steroidal antiandrogen. 212 36

Flutamide is a nonsteroidal pure antiandrogen that acts by inhibiting the uptake and/or binding of dihydrotestosterone to the target cell receptor, thus interfering with androgen action. Flutamide is well absorbed orally and extensively metabolized; its active metabolite, 2-hydroxyflutamide, is formed rapidly and excreted almost entirely by the kidneys. Clinical studies in prostate cancer patients have demonstrated efficacy with flutamide monotherapy in patients who had received no prior treatment, in untreated patients with combined androgen blockade concomitantly with a luteinizing hormone-releasing hormone (LHRH)-agonist, and in relapsed patients. A randomized, placebo-controlled trial demonstrated a 26 percent increase in median survival for patients treated with leuprolide plus flutamide compared with leuprolide plus placebo. When given as monotherapy and in combination with an LHRH-agonist, flutamide is well tolerated. The usual adverse effects are gynecomastia and mild diarrhea when given as a single agent. In combination with an LHRH-agonist, hot flashes, loss of libido, impotence, mild nausea and vomiting, gynecomastia, and diarrhea are commonly reported. However, only diarrhea occurred more frequently in patients treated with leuprolide plus flutamide than in those treated with leuprolide plus placebo. Flutamide is indicated in combination with an LHRH-agonist (e.g., leuprolide) as initial therapy in metastatic (stage D2) prostate cancer. The usual dose is 250 mg po tid given at eight-hour intervals and started concurrently with the LHRH-agonist. Formulary addition is recommended.
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PMID:Flutamide: an antiandrogen for advanced prostate cancer. 219 61

Six patients who had been treated with diethylstibestrol (DES) for prostatic cancer had symmetrical breast uptake of Ga-67. Of these patients, five proved to have DES-induced gynecomastia. The minimum dose and administration period of DES required for Ga-67 uptake in gynecomastia is discussed.
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PMID:Ga-67 uptake in diethylstilbestrol-induced gynecomastia. Experience with six patients. 227 29

Between 1977 and 1986, 11 patients with painful gynecomastia after DES therapy were referred for palliative radiotherapy. The treatment regimens varied from 20 Gy in 5 fractions to 40 Gy in 20 fractions. All 11 patients had satisfactory pain relief on follow-up. All 7 patients who had more than 6 months follow-up had complete relief of mammalgia. The average interval between completion of radiotherapy to complete relief of mammalgia was 3.6 months. This study revealed that radiotherapy is highly effective in palliating mammalgia associated with gynecomastia after DES therapy in prostate cancer patients.
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PMID:Effective radiotherapy in palliating mammalgia associated with gynecomastia after DES therapy. 245 32

The authors describe the abnormalities of gonadal function developing in a patient with prostate cancer who had received estrogen therapy continuously for 6 years. The pretreatment prostate biopsy showed well developed acini consistent with normal androgenization and adenocarcinoma. Twelve years later, 6 years after discontinuation of estrogen treatment, the patient presented with severe hypogonadism, gynecomastia, and primary hypothyroidism. Testicular biopsies showed ghosts of seminiferous tubules with absence of Leydig cells, and prostatic biopsies showed atrophic acini without evidence of malignancy. Despite undetectable serum testosterone levels, serum gonadotropins were inappropriately normal and responded minimally to gonadotropin-releasing hormone (GnRH) administration. Replacement therapy with levothyroxine did not correct gonadal dysfunction. Thus, prolonged estrogen therapy may result in irreversible testicular destruction and loss of the feed-back response of the hypothalamic pituitary gonadal axis.
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PMID:Hypogonadism following long-term treatment with diethylstilbestrol. 250 19

Twenty-two patients with newly diagnosed advanced prostatic cancer treated with once-monthly subcutaneous injection of a long acting depot preparation of a new luteinizing hormone-releasing hormone superagonist (ICI 118,630) with a minimum follow-up duration of 6 months are reported. The partial regression rate was 45.4% while 36.4% of the patients had stable disease and only 18.2% have progressed by P.O.N.CA.P. criteria. Patient acceptance was excellent and side effects occurring during treatment (hot flashes, gynecomastia, etc.) were minimal. The depot preparation of the LH-RH analogue was well tolerated and no side effects required dose modifications or removal from the study. Depot LH-RH analogue may become an alternative treatment for patients with advanced prostatic cancer if further clinical evolutions will confirm that the response rate with LH-RH analogue is comparable to the conventional endocrine therapies.
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PMID:[Treatment of advanced prostatic carcinoma with a depot LH-RH analog (ICI 118630)]. 252 15

Flutamide is a non-steroidal antiandrogenic drug devoid of hormonal agonist activity. Flutamide appears to be a specific antiandrogen only at androgen-dependent accessory genital organs. Its pharmacological activity is due substantially to the principal metabolite, 2-hydroxyflutamide. In comparative trials involving small numbers of patients with previously untreated advanced prostatic cancer, flutamide 750mg daily is comparable with stilboestrol 1 or 3mg daily and with estramustine 560 or 840mg daily. Treatment of newly diagnosed advanced prostatic cancer with flutamide plus a luteinising hormone releasing hormone (LHRH) agonist has produced very promising results, and appears to prolong survival relative to that achieved with leuprolide alone. However, these results require confirmation in suitably designed prospective studies. In previously treated patients refractory to castration, flutamide 750mg daily appears comparable in efficacy to estramustine phosphate 600 mg/m2 daily. Apart from a high incidence (34 to 100%) of gynaecomastia flutamide monotherapy is usually well tolerated, and has the advantage of preserving libido and sexual potency in at least 80% of patients. Gynaecomastia is infrequent, however, when flutamide is used in conjunction with surgical castration or an LHRH agonist. Thus, flutamide is a suitable alternative to other systemic treatment in patients with advanced prostatic cancer who wish to preserve sexual potency. In combination with an LHRH agonist flutamide may become a first-line agent for previously untreated patients with cancer of the prostate.
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PMID:Flutamide. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in advanced prostatic cancer. 267 May 15


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