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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer of the prostate gland is the most frequently occurring malignant lesion in men. Because most prostate cells depend on androgen for growth, removal of testosterone by either orchiectomy or medical castration using diethylstilbestrol or a luteinizing hormone-releasing hormone (LHRH) analogue is first-line treatment for patients with symptomatic Stage D2 disease. The trend in hormonal therapy has been toward long-acting minimal-dosing high-compliance regimens, capitalizing on the recent availability of the long-acting LHRH analogues, which require only monthly injections to maintain castration levels of testosterone, and the nonsteroidal antiandrogen ICI 176,334, which (in early clinical trials) appears to block intracellular testosterone activity with a once-a-day oral regimen. To eliminate the rapid LH increase that can occur during early agonist therapy, combinations of LHRH analogues and antiandrogens (total androgen blockade) have been tested and appear promising. The effects of hormonal treatment in patients with symptomatic Stage D2 prostate cancer have been studied extensively and are relatively well understood. By contrast, hormonal treatment has not been explored in contemporary randomized Phase III trials of asymptomatic Stage D2, D1, or C disease, localized Stage B or A disease, or before prostate surgery or radiation treatment. Research must continue to determine the optimal regimen that suppresses testosterone activity with the least amount of toxicity.
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PMID:Recent developments in endocrine treatment of prostate cancer. 138 83

In 20 patients with locally advanced or metastatic prostate cancer, testicular tissue obtained by bilateral subcapsular orchidectomy was examined for steroid hormone content and morphological changes. Eight patients (group I) had not received previous treatment. Twelve patients had been treated with monthly subcutaneous doses of the depot luteinizing hormone-releasing hormone (LHRH) agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630). Six patients (group II) had been treated for less than 6 months and 6 patients (group III) for more than 6 months. The longest duration of treatment with depot LHRH was 36 months. After 2 months of treatment (group II), maximum hormone suppression was achieved and remained unchanged even if treatment was continued for 3 years. The mean serum testosterone levels were decreased in group II (means = 0.586 mg/ml) and in group III (means = 0.575 mg/ml) and were found to be in the range of castration; a statistically significant reduction in luteinizing hormone (P less than 0.000001) and follicle-stimulating hormone (P less than 0.05) was observed in the treated patient groups. The content of the steroid hormones dihydroepiandrosterone sulfate (DHEA)-S, testosterone, androstenedione, oestradiol, progesterone and 17-alpha-hydroxyprogesterone/g testicular tissue was significantly lower in patients on LHRH agonists. The differences in concentration were particularly pronounced for DHEA-S, T and A. As in the case of serum concentrations, the testicular tissues showed no differences between groups II and III. In the treated groups a significant reduction in weight was seen, depending on the duration of therapy. Similarly, the structural changes visible by the aid of light and electron microscopes increased with the duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the duration of therapy with the LHRH agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630) on the steroid hormone content and the morphology of human testicular tissue in the treatment of patients with advanced prostate cancer. 182 57

One hundred eighteen patients with stage D (D1 or D2) prostate cancer with a mean age of 69 years were treated with monthly goserelin (Zoladex; ICI 118, 630; ICI Americas Inc, Wilmington, DE, property of Imperial Chemical Industries PLC) injections and the data were analyzed for predictive parameters for best response and time to treatment failure (National Prostatic Cancer Project [NPCP] and Eastern Cooperative Oncology Group [ECOG] criteria). For best response in a univariate analysis, the performance status (PS 0-1 v 2-3) (P = .01), hematocrit (P = .04), and pain (P = .04) were significant. For time to treatment failure by univariate analysis, ECOG performance status (0-1 v 2-3) was most predictive (P less than .0001), followed by pain at entry (P = .0002), initial testosterone (T) level (greater than 250 ng/dL) (P = .0005), age less than 69 years (P = .02), alkaline phosphatase (less than 115 IU/L) (P = .03), hemoglobin (less than 14 g/dL) (P = .03), whereas normal acid phosphatase (less than 3 IU/mL) (P = .29) was not predictive. In multivariate analysis for time to treatment failure, only the ECOG performance status was of significance (P = .01). Estimated median time to treatment failure for PS of 0-1 was 88 weeks and for PS of 2-3 was 31 weeks.
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PMID:Predictive initial parameters for response of stage D prostate cancer to treatment with the luteinizing hormone-releasing hormone agonist goserelin. 213 2

Orchiectomy was performed in 16 patients because of progression of prostatic cancer despite adequate medical castration with goserelin (Zoladex, ICI) over a mean period of 17.6 months. Severe tubular atrophy was seen in the testes. The Leydig cells also showed signs of atrophy, a fact that may indicate a direct effect of goserelin on these cells. In 1 patient, however, orchiectomy was postponed for 3 months after cessation of medical castration. The serum testosterone had resumed almost normal values and testicular histology revealed intact spermatogenesis and apparently normal Leydig cells.
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PMID:Testicular histology after treatment with LH-RH analogue for carcinoma of the prostate. 214 Feb 82

Following promising results in animal studies, Casodex (ICI 176,334) has been studied in the treatment of patients with advanced prostate cancer. At doses of 10, 30 and 50 mg, the drug was found to be well tolerated, with a moderate effect on sex hormone levels. The 50 mg dose of Casodex (daily) reduced previously elevated acid phosphatase levels by 50% or more in 71% of patients.
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PMID:Casodex (ICI 176,334), a new, non-steroidal anti-androgen. Early clinical results. 251 47

The identification of the decapeptide luteinizing hormone-releasing hormone (LHRH) has led to the development of LHRH agonists, which are a new class of drugs for the treatment of advanced prostate cancer. These peptides have a modified amino acid structure that makes them more potent than LHRH. Prolonged administration of LHRH agonists results in down-regulation of the LHRH receptors in the pituitary and decreased secretion of luteinizing hormone. The result is decreased production of testosterone by Leydig cells, which is the basis for the use of LHRH agonists to treat prostate cancer. The effectiveness of LHRH agonists has been demonstrated in the United States in several randomized, controlled clinical trials. Daily administration of leuprolide produced equivalent results compared with diethylstilbestrol (DES). More recently, in two separate, randomized studies, the long-acting LHRH agonist Zoladex (ICI Pharma, Wilmington, Delaware) produced the same objective response rate as DES or bilateral orchiectomy. The equivalent response rates obtained with LHRH agonists indicate that these drugs can now be considered a reasonable treatment option for patients with metastatic prostatic cancer.
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PMID:Luteinizing hormone-releasing hormone (LHRH) agonists for treatment of advanced prostatic carcinoma. 252 10

Two multicenter, open, randomized phase III clinical trials were conducted in the United Kingdom to compare the effectiveness and safety of the depot formulation of the luteinizing hormone-releasing hormone (LHRH) agonist goserelin (Zoladex, ICI Pharma, Wilmington, Delaware), 3.6 mg sc/28 d, with orchiectomy and with diethylstilbestrol (DES), 1 mg tid, in the treatment of advanced prostatic cancer. In the Zoladex versus orchiectomy trial, there was no significant difference between the treatment groups with regard to subjective and objective responses (British Prostate Group criteria), endocrine responses, clinical effects and side effects, time to treatment failure and death, or survival after similar median follow-up periods. It was concluded that depot Zoladex had behaved as a truly medical alternative to orchiectomy. In the Zoladex versus DES trial, subjective and objective responses (British Prostate Group and National Prostatic Cancer Project criteria), response duration and survival were similar. However, there was a more rapid response to treatment in the depot Zoladex group. Side effects from Zoladex such as flare symptoms during the initial stages of treatment required no discontinuation of therapy; in contrast, 15 percent of patients receiving DES required cessation of therapy during the first three months because of side effects. It was concluded that depot Zoladex was superior to DES in its attainment of an early objective response and in its absence of side effects, and that Zoladex was comparable with DES in terms of response rates and survival.
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PMID:Phase III studies to compare goserelin (Zoladex) with orchiectomy and with diethylstilbestrol in treatment of prostatic carcinoma. 252 11

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

The relative merits of the steroidal anti-androgen, cyproterone acetate, and the non-steroidal anti-androgens flutamide and nilutamide, are reviewed. It is concluded that pure anti-androgens offer some advantages over cyproterone acetate but that they each have some features which merit improvement. A new compound which was a pure anti-androgen, peripherally selective, well tolerated with a long half-life would have significant advantages. Preclinical studies in rats and dogs show that Casodex (ICI 176,334) is a potent pure anti-androgen which is well tolerated and has a long half-life. Casodex induces marked regression of the prostate yet fails to cause the substantial elevation in serum LH and testosterone seen with flutamide and nilutamide; it is thus peripherally selective. Casodex is as effective as surgical or medical castration with Zoladex in limiting the growth of the transplantable androgen-responsive Dunning rat prostate tumour. Such a profile makes Casodex a strong candidate as the future anti-androgen of choice for the treatment of prostate cancer and benign prostate hypertrophy.
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PMID:"Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies. 253 59

Win 49596 is a new orally active, steroidal androgen receptor antagonist. Win 49596 inhibited ventral prostate, seminal vesicle and levator ani weight gain in either 5 alpha-dihydrotestosterone (DHT) or testosterone propionate-treated castrated, immature male rats. In intact, adult male rats, Win 49596 significantly inhibited weight gain by the ventral prostate, dorsal lateral prostate and seminal vesicles, but not the testes at doses as low as 50 mg/kg/day x 14 p.o. However, daily oral administration of equivalent antiandrogenic doses of either Win 49596, ICI 176,334, or flutamide for 14 days to mature, intact male rats resulted in elevations of circulating testosterone of approximately 3-, 2-, and 10-fold, respectively. At doses as high as 400 mg/kg p.o., Win 49596 did not have androgenic, progestational, estrogenic or antiestrogenic activity in rat or rabbit models. However, in the Clauberg assay, Win 49596 did have weak antiprogestational activity at doses of 25-400 mg/kg/day p.o. These data indicate that Win 49596 is a peripherally selective antiandrogen that has minimal effects on circulating testosterone levels and is devoid of hormone agonist activity. Thus, Win 49596 may be useful for the treatment of androgen dependent conditions such as benign prostatic hyperplasia and prostatic cancer.
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PMID:Endocrine profile of Win 49596 in the rat: a novel androgen receptor antagonist. 261 57


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