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)

We have conducted a double-blind comparative study of flutamide and chlormadinone acetate (CMA) on patients with stage C or D prostatic cancer and with no prior experience of hormone therapy. This is believed to be the first such trial entered in the medical literature, fifty-four patients were randomly selected to undergo flutamide (p.o.) monotherapy at a daily dose of 375 mg, which was determined as the optimal dose in Japan in our previous phase II study. Forty-nine others were randomly selected to undergo CMA (p.o.) monotherapy at a daily dose of 100 mg, which is the most commonly used dosage in Japan for patients with prostatic cancer. Ultimately, 47 patients from the flutamide group and 40 patients from the CMA group were judged eligible, with efficacy being evaluated after 12 weeks of treatment. Similar objective responses were seen in both groups: 48.9% (95% confidence limits 34.1-63.9%) in the flutamide group, 45% (95% confidence limits 29.3-61.5%) in the CMA group. The response at each organ site was also similar between the groups. Serum prostatic specific antigen decreased by more than 50% of the abnormal pretreatment level in 87.5% of the flutamide group and in 85.7% of the CMA group. Serum luteinizing hormone, follicle-stimulating hormone, testosterone and 5 alpha-dihydrotestosterone decreased significantly in the CMA group, but increased significantly in the flutamide group. The serum testosterone level after 12 weeks of treatment was 0.955 +/- 0.13 ng/ml in the CMA group and 6.64 +/- 0.38 ng/ml in the flutamide group. The serum estradiol level also increased significantly in patients in the flutamide group. The serum prolactin level decreased significantly in the flutamide group, but increased significantly in the CMA group. Eight patients on flutamide manifested gynecomastia. Diarrhea and hepatic toxicity were observed in both groups, but only rarely, and were well tolerated. We have thus concluded that flutamide is as effective as CMA in maintaining libido and potency without decreasing testosterone levels.
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PMID:A randomized phase II trial of flutamide vs chlormadinone acetate in previously untreated advanced prostatic cancer. The Japan Flutamide Study Group. 768 29

Observations that serum follicle-stimulating hormone (FSH) levels begin to rise after initial suppression during chronic gonadotropin-releasing hormone (GnRH) agonist treatment of men with prostate cancer had led to speculation that FSH escape might in part account for the failure of GnRH agonist analogs to completely suppress spermatogenesis in normal eugonadal men. However, previous studies in healthy young men failed to report FSH escape during GnRH agonist treatment for up to 16 weeks. We considered the possibility that this may have been due to the insensitivity of the FSH assays. Accordingly, using highly sensitive and specific two-site directed fluorometric assays and a sustained-release GnRH agonist formulation, we reexamined the issue of whether serum FSH levels rise after initial suppression during chronic GnRH agonist treatment. Two groups of healthy normal men, 19-50 years of age, received 7.5 mg of a long-acting GnRH agonist microcapsule formulation (Lupron Depot; TAP Pharmaceutical Company, North Chicago, Illinois) on days 1 and 30. In addition, the subjects received either 4 or 8 mg/day testosterone replacement by means of a testosterone microcapsule injected intramuscularly on day 1. Serum luteinizing hormone (LH) and FSH levels were measured by sensitive and specific two-site directed fluorometric assays on multiple occasions during the 3-week control period and the 9-week treatment period. Serum LH levels declined to a nadir between 2 and 4 weeks and stayed suppressed throughout the remainder of the treatment period in both the 4- and 8-mg testosterone groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Follicle-stimulating hormone (FSH) escape during chronic gonadotropin-releasing hormone (GnRH) agonist and testosterone treatment. 786 Apr 18

A population-based nested case-control study was conducted to determine the relation of prediagnostic serum levels of testosterone, dihydrotestosterone, prolactin, follicle-stimulating hormone, luteinizing hormone, estrone, and estradiol to the risk of subsequent prostate cancer. Serum specimens of study subjects were available from a blood collection campaign in Washington County, Maryland, in 1974. Serum hormone levels of 98 histologically confirmed prostate cancer cases diagnosed in the subsequent 13 years were compared to those of 98 controls who were individually matched to cases on the basis of age (within weeks), sex, and race. There were no significant differences in levels of these hormones between cases and controls, although elevated levels of luteinizing hormone and of testosterone:dihydrotestosterone ratios were associated with mild increased risks of prostate cancer.
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PMID:Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer. 842 Jun 7

Prostate inhibin peptide (PIP) is a follicle-stimulating hormone (FSH) regulating peptide produced by the prostate. The mechanism of its endocrine role in regulating prostate growth is believed to be androgen-independent but FSH-dependent. Previous studies using polyclonal antibody proposed PIP as a prostatic-specific marker in cancer diagnosis. However, the recently available monoclonal antibody has not yet been evaluated. Paraffin sections of 72 prostatectomy specimens for prostate cancer with or without hormonal blockage therapy and 10 nonneoplastic prostate tissues from autopsy were stained by using PIP monoclonal antibody (clone: 4A6A6) with the avidin-biotin complex method. PIP reactivity was semiquantitatively estimated in prostatic carcinoma (PCA), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal tissue in each case when ever present. Statistical analyses were performed accordingly. PIP expression is predominantly cytoplasmic. Urothelium, seminal vesicles, inflamed prostatic glands, basal cells, and squamous metaplasia were negative for PIP. Average percentage of cells expressing PIP was significantly decreased in PIN (40%) and PCA (14%) when compared with BPH (81%) and normal tissue (68%). There was no correlation of tumor PIP level with patient's age, tumor size, Gleason score, tumor stage, or the usage of preoperative hormonal blockage therapy. PIP monoclonal antibody should be used with caution as a prostate-specific marker in surgical pathology. The mechanism for this alteration and the effect of PIP on prostatic tumor growth, particularly in patients under a variety of hormonal therapies, needs further study.
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PMID:Decreased immunoexpression of prostate inhibin peptide in prostatic carcinoma: a study with monoclonal antibody. 1002 44

Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on low-dose EMP as first-line monotherapy. The study found that the mean serum prostate-specific antigen level decreased to within the normal range by day 50; mean serum testosterone, leutinizing hormone and follicle-stimulating hormone reduced to undetectable levels by day 20; and mean serum estradiol increased to a very high level within 1 week. These data implicate that low-dose EMP can suppress quickly and adequately the pituitary-gonadal axis, although the antitumor effect has not as yet been elucidated. For these reasons, it is necessary to re-evaluate low-dose EMP monotherapy in previously untreated advanced prostate cancer.
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PMID:Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer. 1124 Aug 22

The natural history of prostate cancer has long been related to the male hormone testosterone, and treatment has focused on depletion of this androgen to slow or prevent growth of prostate cancer tissue. It has become clear recently, however, that more than androgens influence the progression of prostate cancer, with recent interest focusing on the gonadotropin, follicle-stimulating hormone (FSH). Research of the last decade has found that FSH is produced in and FSH receptors are expressed in the prostate. Investigators have found as well that production of FSH is altered in prostate cancer: FSH levels are increased and receptor production raised in the cancerous prostate. It also has been shown that there are endogenous compounds such as prostatic inhibin peptin that can modulate FSH levels. All of these findings are outlined in this paper, and suggest that FSH may affect the pathogenesis and progression of prostate cancer and that altering FSH production may prove to be an active therapeutic maneuver.
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PMID:Humoral mechanisms in prostate cancer: A role for FSH. 1141 18

Luteinizing hormone-releasing hormone (LHRH) antagonists work by directly inhibiting LHRH without any initial stimulation of the LHRH receptor. The physiologic response is a direct and rapid decrease in luteinizing hormone, follicle-stimulating hormone, and testosterone without any flare. Although there has been extensive basic-science work on these medications, practical shortcomings have limited clinical studies in prostate cancer. Many of these compounds induce significant histamine-mediated side effects, and until recently, no depot form existed. In 2 recent phase-3 studies comparing abarelix depot with leuprolide and with leuprolide plus bicalutamide, abarelix lowered serum testosterone more quickly. None of the 89 patients on leuprolide alone were castrate on day 8 as opposed to 72% of the 180 patients randomized to abarelix (P <0.001). Similarly, none of the combination group were castrate by day 8, whereas 68% of the abarelix patients were castrate (P <0.001). In addition, 82% of the patients treated with leuprolide and 86% of those given leuprolide/bicalutamide had testosterone surge, whereas none of the abarelix patients did (P <0.001 for both studies). Both phase 2 and phase 3 data show abarelix to be well tolerated. In conclusion, LHRH antagonists offer the physiologic response of orchiectomy without surgery. These medications are well tolerated and a depot form now exists. The expansion of indications for androgen deprivation, such as downsizing or intermittent therapy, could provide many opportunities for their use. Despite these encouraging advances, however, their routine use for advanced prostate cancer may depend on demonstration of a survival advantage in avoiding flare.
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PMID:Luteinizing hormone-releasing hormone antagonists in prostate cancer. 1150 41

This study was carried out to evaluate the possible long-term endocrine effect of short-term neoadjuvant leuteinizing hormone-releasing hormone analogue (LHRHa) administration in localized prostate cancer. A total of 419 men were treated for 3-6 months at The Royal Marsden NHS Trust by neoadjuvant androgen suppression using monthly depot injections of LHRHa before radical radiotherapy. Serum testosterone (852 measurements), leuteinizing hormone (LH) (799 measurements), and follicle-stimulating hormone (FSH) levels (801 measurements) were grouped according to their timing in relation to hormonal treatment and then analysed. Suppression of pituitary gonadotrophins and testosterone after the administration of LHRHa and their recovery after cessation of the drug was clearly observed. Median serum testosterone levels decreased from 16 nmol/l to 14 nmol/l when comparing prehormonal and follow-up phases. The same comparison showed an increase in median serum LH and FSH levels, with the median LH rising from 5 u/l to 8 u/l and the median serum FSH rising from 6 u/l to 20 u/l. On long-term follow-up, three of 256 men have remained with testosterone levels in the castrate range. Similar highly significant results were seen in subgroup of 103 men who had both pre-LHRHa and follow-up hormone levels analysed (P=0.012, P<0.001, P<0.001 for testosterone, LH and FSH respectively). Our data suggest the possibility of residual gonadal dysfunction after short-term LHRHa administration and radical radiotherapy in localized prostate cancer. Serum testosterone levels are restored to normal levels in the majority of patients, with a compensatory increase in serum levels of LH.
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PMID:Recovery of serum testosterone, LH and FSH levels following neoadjuvant hormone cytoreduction and radical radiotherapy in localized prostate cancer. 1155 28

Pulsatile gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH) and thus controls the hormonal and reproductive function of the gonads. Blockade of GnRH effects may be wanted for a variety of reasons-eg, to prevent untimely luteinisation during assisted reproduction or in the treatment of sex-hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. Only recently have GnRH-receptor antagonists, that immediately block GnRH's effects, been developed for clinical use with acceptable pharmacokinetic, safety, and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All current indications for GnRH-agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence so far has been in assisted reproduction and prostate cancer.
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PMID:Gonadotropin-releasing-hormone-receptor antagonists. 1173 58

Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved.
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PMID:Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis. 1179 Feb 81


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