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)

Superactive GnRH agonists represent a new class of pharmacologic agents that inhibit reproductive function in both men and women when administered chronically. These hormonal drugs are being tested extensively as both male and female contraceptive agents, as a treatment for prostate cancer, and as a new treatment for idiopathic precocious puberty. Other potential uses include treatment for endometriosis, hirsutism, polycystic ovarian disease, and severe intractable androgen-related acne. This chapter reviews the effects of GnRH agonists on gonadotropin and steroid hormone secretion in both men and women, and assesses the potential of these agents in the varied clinical uses delineated above.
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PMID:Superactive gonadotropin-releasing hormone agonists. 634 74

Gonadotropin-releasing hormone agonists are a relatively new class of drugs, which, when chronically administered, result in marked reductions in blood levels of testosterone and estrogen. These drugs include leuprolide acetate (Lupron); the first GnRH agonist to be approved in the United States, nafarelin acetate (Synarel); and goserelin acetate (Zoladex). Approved indications for these drugs, depending on the specific agent, include advanced prostate cancer, endometriosis, and precocious puberty. These and other investigational GnRH agonists are also being evaluated in many other diseases, including uterine fibroids, polycystic ovarian disease, breast cancer, fibrocystic breast disease, benign prostatic hypertrophy, and irritable bowel syndrome. Because of their therapeutic potential in many endocrinologic disorders, the GnRH agonists represent one of the most important advances in hormonal therapy in the past few decades. Thus, it appears likely that in the 1990s a greater number of patients will be receiving these agents. This article summarizes the application of GnRH agonist drugs in clinical practice, their side effects, and important information for patient use.
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PMID:Uses of GnRH agonists. 799 7

Analogues of luteinizing hormone-releasing hormone (LH-RH) have made possible new approaches to the treatment of some hormone-dependent cancers and diseases and conditions which result from inappropriate sex hormone levels. In the fields of both gynaecology and oncology, the development of sustained delivery depot systems has played a key role in the clinical use of LH-RH agonists and will be also essential for the LH-RH antagonists. Clinical results show that therapy with agonists of LH-RH is the preferred method of treatment for men with advanced prostate cancer. For prostate cancer and other indications, the new LH-RH antagonists such as Cetrorelix may offer an advantage based on the fact that they inhibit LH, FSH and sex-steroid secretion from the start of the administration and thus reduce the time of the onset of therapeutic effects. The use of antagonists would avoid the temporary clinical "flare-up" of the disease which can occur with the agonists in men with prostate cancer. The rapid shrinkage of the prostate and improvement in urinary symptoms obtained with Cetrorelix in men with benign prostatic hyperplasia (BHP) suggests that LH-RH antagonists offer a therapeutic alternative in patients who are considered poor surgical risks. Various experimental and clinical studies suggest that analogues of LH-RH might be useful for treatment of premenopausal women with oestrogen-dependent breast cancer. LH-RH antagonists such as Cetrorelix could be also considered for hormonal therapy of epithelial ovarian cancer which responds only marginally to the agonists, and for treatment of endometrial cancer. Many investigators have reported beneficial effects of LH-RH agonists in the treatment of patients with leiomyomas. LH-RH antagonists also appear to be promising for therapy of uterine leiomyomas, and in addition might be useful for treatment of endometriosis and polycystic ovarian disease (PCOD). LH-RH agonists have been employed in in vitro fertilization and embryo transfer (IVF-ET) programs to prevent a premature rise in LH and various results suggest that the use of antagonist Cetrorelix in assisted reproduction procedures, could be even more advantageous. For most of these indications, the use of sustained release depot preparations will be required.
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PMID:Rational use of agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH) in the treatment of hormone-sensitive neoplasms and gynaecologic conditions. 1083 70

Decisions on policies for screening for prostate cancer require that information upon health-related quality of life (HRQL) and cost-effectiveness (CE) be available, as the lead time for some of the cases detected by screening will be very long and detriments in quality of life could have a major impact on the subjects remaining life-span. A framework within which both HRQL and cost-effectiveness of prostate cancer screening can be assessed is presented. Studies of both are ongoing in the European Randomised Study of screening for prostate cancer and the US Prostate, Lung, Colon and Ovary trial. Preliminary information confirms that it is important to study screened subjects and controls, and not to assume that inferences derived from study of prostate cancer outside screening trials can be extrapolated to the trials. However, it will require prolonged study to enable the overall effects on quality of life, and on cost-effectiveness to be determined. Such studies are ongoing for the two trials.
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PMID:Health-related quality of life and cost-effectiveness studies in the European randomised study of screening for prostate cancer and the US Prostate, Lung, Colon and Ovary trial. 1167 1

Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.
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PMID:Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial. 1177 70

From 1992-2001, 7 countries in Europe gradually recruited men for the European Randomised Screening for Prostate Cancer (ERSPC) trial. Centres recruit different age groups and have different designs for recruiting and countries have different underlying risks for prostate cancer. Recruitment has reached 163,126 men aged 55-69 at entry now. Our purpose was to calculate the power of the trial and at what point in time can statistically significant differences in prostate cancer mortality be expected. Recruitment data were collected from the screening centres. We calculated the expected number of prostate cancer deaths in each follow-up year, based on national statistics and expected rate in trial entrants. The power was calculated using different assumptions on intervention effect and contamination rate and also if the ERSPC trial would cooperate with other trials. With an assumed 25% intervention effect in men actually screened and a 20% contamination rate, the trial will reach a power of 0.86 in 2008. With an assumed intervention effect of 40%, the power reaches 0.90 in 2003-2004. Pooling data with those of the Prostate, Lung, Colorectal and Ovary (PLCO) trial early is expected to improve the power to 79% (20% intervention effect) to 92% (40% intervention effect PLCO). Adding more centres with compliance rates lower than 45% decreases the power of the trial. The ERSPC trial has sufficient power to detect a significant difference in prostate cancer mortality between the 2 arms if the true reduction in mortality by screening is 25% or more or if contamination remains limited to 10% if the true effect is 20% or more. If early detection and treatment turns out to have a stronger effect as may be suggested by observational data, the ERSPC trial is likely to conclusively show that within the next 5 years.
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PMID:Prostate cancer mortality reduction by screening: power and time frame with complete enrollment in the European Randomised Screening for Prostate Cancer (ERSPC) trial. 1185 18

The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a large, randomized controlled trial of screening versus control, conducted in eight European countries (Belgium, Finland, France, Italy, the Netherlands, Spain, Sweden, and Switzerland). This article focuses on important aspects relating to recent findings from the ERSPC about two topics: first, leadtime and overdiagnosis, and second, prostate-specific antigen (PSA) as a test for repeated screening. The ERSPC together with the prostate cancer arm of the Prostate, Lung, Colon and Ovary (PLCO) screening trial of the National Cancer Institute in the United States are set to show or exclude an effect of screening on prostate cancer mortality. Both studies are progressing according to plan. Definitive endpoint-related data can be expected between 2005 and 2010 depending on the difference in prostate cancer mortality that may be shown between the screening and control arms. The ERSPC will allow a risk-to-benefit analysis including parameters of quality of life and cost. Overdiagnosis with present prostate cancer screening regimens is high. This amount of overdiagnosis is likely to be unacceptable for most healthcare policy makers and providers. Addressing overdiagnosis will be a major research task for urologists for the years to come. Present screening needs to be more "selective" for cases that have aggressive patterns and are likely to lead to clinical diagnosis of prostate cancer and/or death. The test characteristics of prostate-specific antigen (PSA) change after one use. The positive relation between PSA levels and positive predictive value (PPV) and detection rates in first screening rounds are lost. This may be compatible with the observation that tumor volumes in second round screening are smaller, and larger tumors are harvested. Tumor volume becomes a negative predictor in round 2, indicating that a large proportion of elevated PSA values are caused by benign prostatic hyperplasia (BPH) rather than by prostate cancer. While the outcome of the ongoing randomized studies is uncertain, screening tests cannot be refused to men who are well-informed and accept to take the risk of experiencing more harm than benefit as a result of a positive screening test result.
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PMID:Detection of prostate cancer: the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC). 1578 Jan 57

The chemical characterization of the hypothalamic decapeptide gonadotropin-releasing hormone (GnRH) has stimulated the development of analogues of GnRH with important clinical applications. Chronic administration of the GnRH analogues nafarelin acetate and leuprolide acetate results in an initial stimulation of pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, which is followed by a profound decrease in the secretion of LH and FSH. The decrease in the secretion of LH and FSH produces a hypogonadal state that is associated with an improvement in many sex-steroid-dependent disease processes. The GnRH analogues are clearly effective in the treatment of prostate cancer, endometriosis, uterine myomas, polycystic ovarian disease, and the premenstrual syndrome.
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PMID:Clinical applications of GnRH and its analogues. 1840 75

There continues to be controversy regarding serum Prostate-Specific Antigen (PSA) and prostate cancer screening. We anxiously await the results of two large prospective randomized clinical trials (Prostate, Lung, Colon, and Ovary-PCLO screening trial in the US and European Randomized Study of Screening for Prostate Cancer-ERSPC in Europe) assessing the benefits of prostate cancer screening. However the true question to answer may be which cancer to treat and when should we treat it.
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PMID:Prostate cancer--to screen, or not to screen, is that the question? 1910 47

Screening for prostate cancer by use of serum prostate specific antigen (PSA) remains controversial. In the recent Cochrane analysis, an attempt is made to clarify the issue by conducting a meta analysis of available randomized screening trials. Two large trials are considered to provide data of similar and sufficient quality to conduct a separate meta analysis. However, in the view of this author, this analysis fails because standard Cochrand quality criteria are not observed. Details are given and the outcome suggests that one of the trials, the European Randomized Study of Screening for Prostate Cancer (ERSPC) should be considered superior to the Prostate, Lung, Colon, Ovary screening trial (PLCO) conducted in the USA.
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PMID:ERSPC, PLCO studies and critique of cochrane review 2013. 2453 78


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