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

A randomized, controlled trial of the treatment of metastatic prostatic cancer using either the LH-RH analogue Zoladex or orchidectomy is reported. The trial was conducted in the U.K. and Ireland and involved participants in 17 centers. The design of the trial is outlined and the response criteria discussed. The results show that the patient characteristics in the two treatment groups were comparable upon entry. Repeated administration of Zoladex every 28 days has been shown to be as effective as orchidectomy in lowering serum testosterone to castrate levels. The subjective and objective response rates were similar, as were the duration of response, time to treatment failure, and survival rates. The withdrawals from the trial and adverse reactions are discussed. These results, 10 months after the closure of recruitment to the trial, seem to indicate that Zoladex and orchidectomy are equivalent treatments and that Zoladex seems to be a truly medical alternative to surgical castration. Finally, other ongoing U.K. trials of the treatment of advanced prostate cancer are outlined.
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PMID:U.K. trials of treatment for M1 prostatic cancer. The LH-RH analogue Zoladex vs. orchidectomy. 297 72

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.
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PMID:Interim report of a randomized trial comparing Zoladex 3.6 mg depot with diethylstilbestrol 3 mg/day in advanced prostate cancer. The West Midlands Urology Research Group. 297 73

A multicenter randomized clinical trial was carried out between May, 1986 and May, 1987 involving 82 patients with stage B-D prostatic carcinoma from 29 centers. The clinical efficacy, endocrine effect, safety and usefulness of the luteinizing hormone-releasing hormone (LH-RH) analogue and other endocrine manipulations in the treatment of prostatic carcinoma. Zoladex depot containing 3.6 mg of ICI 118,630, an LH-RH analogue, was administered every four weeks 3 times in total. Patients in the control group received either 300 mg of diethylstilbestrol diphosphate orally daily for 12 weeks or orchidectomy. An antitumor effect (CR + PR) was observed in 21 of the 33 patients (63.6%) in the Zoladex group and in 22 of the 33 (66.7%) in the control group, showing no significant difference between the two groups. There was no significant difference in overall subjective response either; 21 of the 24 (87.5%) in the Zoladex group and 24 of the 30 (80.0%) in the control group. In both groups, 100% endocrine effect was obtained as shown by achievement of castration in all patients. Adverse reactions were observed in 14 of the 39 (35.9%) patients treated with Zoladex as compared with 19 of the 34 (55.9%) control patients, resulting in no significant difference in the incidence between the two groups. These adverse reactions were not so severe as to require withdrawal from the study. In both groups, the treatment was assessed as slightly or more useful in 29 of the 33 (87.9%) patients. From these results, it is concluded that Zoladex, 3.6 mg depot, is a useful drug for treatment of prostatic cancer, having clinical efficacy and endocrine effects comparable to those of the conventional endocrine manipulations, being safe, and causing less physiological and psychological pain.
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PMID:[Endocrine therapy for prostatic carcinoma--the clinical trial to compare the efficacy of LH-RH analogue, ICI 118630 (Zoladex) with castration or estrogen]. 297 27

A study was conducted of the response of the pituitary-testicular axis to two different methods of administration of the luteinising hormone releasing hormone (LHRH) analogue ICI 118630 (Zoladex) in patients with prostatic cancer. The analogue was given by continuous infusion to four previously untreated patients with prostatic cancer for 60 days (group 1). Subsequently a further four patients were given a depot formulation of the same analogue by subcutaneous injection once every 28 days (group 2). Both methods of administration produced similar, successful suppression of luteinising hormone (LH) associated with a reduction of testosterone to castrate concentrations. The median basal testosterone concentrations before treatment in groups 1 and 2 were 20.6 and 14.1 nmol/l (5.94 and 4.07 ng/ml) respectively; these were reduced to 1.4 and 1.1 nmol/l (0.40 and 0.32 ng/ml) within four weeks of the start of treatment. The median basal LH concentration in groups 1 and 2 were 7.9 and 16.6 IU/1 respectively, which were suppressed to 2.6 and 2.4 IU/1 by four weeks. The suppression of LH and testosterone was maintained with continuous subcutaneous infusion for up to 60 days in group 1, and by subsequent injections of the depot every 28 days in group 2. The use of depot preparation of an LHRH analogue to suppress gonadotrophin and sex hormone secretion offers the convenience of once monthly injections when LHRH analogues are required for the long term treatment of elderly patients with prostatic cancer and children with precocious puberty.
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PMID:Preliminary report on use of depot formulation of LHRH analogue ICI 118630 (Zoladex) in patients with prostatic cancer. 315 36

The luteinizing hormone releasing hormone, Zoladex, has been used in three centres, Pontefract, Antwerp and Mistelbach, to treat carcinoma of the prostate. An initial protocol using a soluble daily injection has been followed by a second study employing a monthly administered depot preparation. After an initial stimulation it has been shown that both daily and monthly injections reduce plasma testosterone to castrate levels. Circulating luteinizing hormone levels are also initially stimulated and then suppressed. Treatment toxicity has been minimal and in these short term studies reduction of acid phosphatase and subjective and objective tumour responses have been similar to those expected from effective hormonal therapy of prostatic cancer.
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PMID:An LH-RH analogue (Zoladex) in the management of carcinoma of the prostate: a preliminary report comparing daily subcutaneous injections with monthly depot injections. 315 98

In a prospective, randomized open study, a long-acting LHRH agonist (Zoladex) was compared with polyoestradiol phosphate (Estradurin), both widely used in Finland for palliative treatment of prostatic carcinoma, as regards efficacy and side effects. Of the 236 enrolled patients, 129 were randomized to receive LHRH agonist and 107 to oestrogen treatment. The median follow-up was 25 months. Reduction of prostatic volume was quicker and more effective in the LHRH than in the oestrogen group, and serum testosterone concentrations fell to castration level after 1 month and 1 year, respectively. In locally advanced (M0) and histologically well or moderately differentiated tumours, LHRH agonist therapy was considerably more effective than oestrogen as regards time to progression of the carcinoma, but in metastatic (M1) and histologically poorly differentiated tumours both methods gave similar results. Cardiovascular complications showed equal incidence in both groups. LHRH agonist therapy thus seemed to be more effective than polyoestradiol phosphate against locally advanced prostatic cancer in the doses used.
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PMID:Comparison of a long-acting LHRH agonist and polyoestradiol phosphate in the treatment of advanced prostatic carcinoma. An open prospective, randomized multicentre study. 793 68

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

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.
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PMID:Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy. 801 57

The therapeutic options for the treatment of androgen-independent prostatic cancers are rather limited; this is mainly because our understanding of the local mechanisms involved in the control of androgen-independent proliferation of the tumor is still very poor. The present experiments have been performed to verify whether luteinizing hormone-releasing hormone (LHRH) agonists may possess a direct effect on the growth of the human androgen-independent prostate cancer cells DU 145 and whether a LHRH growth regulatory system may be present in these cells. The data have shown that two potent LHRH agonists (Zoladex and Buserelin) exert a significant and dose-dependent antiproliferative action on DU 145 cells, after 4 days of treatment. The inhibitory action of Zoladex and Buserelin is completely counteracted by the simultaneous treatment of the cells with a potent LHRH antagonist, suggesting that the action of the LHRH agonists may be mediated by specific receptors. This hypothesis has been confirmed by the demonstration that low-affinity binding sites for 125I-Buserelin are present on DU 145 cell membranes, particularly when cells are cultured in serum-free conditions. By using the reverse transcription-polymerase chain reaction technique, in the presence of a pair of specific oligonucleotide primers complementary to the human LHRH complementary DNA, it has been demonstrated that a mRNA for LHRH is expressed in DU 145 cells. Taken together, these data seem to indicate that an autocrine/paracrine LHRH (or LHRH-like) loop is present in androgen-independent prostate cancer cells, and may participate in the regulation of tumor cell growth. To verify this hypothesis, DU 145 cells have been cultured in serum-free conditions, and treated with a LHRH antagonist for 4 days. The treatment resulted in a significant increase of cell proliferation, suggesting an inhibitory role for the LHRH system in the local regulation of cell growth. In conclusion, these data demonstrate that: (a) LHRH agonists exert a specific antiproliferative action on the human androgen-independent DU 145 cells; (b) an autocrine/paracrine LHRH (or LHRH-like) loop, which seems to be inhibitory on cell proliferation, is expressed in DU 145 cells.
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PMID:Antiproliferative effects of luteinizing hormone-releasing hormone (LHRH) agonists on human androgen-independent prostate cancer cell line DU 145: evidence for an autocrine-inhibitory LHRH loop. 803 42

Androgen ablation by bilateral orchiectomy or by the administration of gonadotropin-releasing hormone (GnRH) agonists has become standard treatment for advanced prostate cancer. However, serum levels of dihydrotestosterone (DHT) remain at about 40% of the precastration levels due to the conversion of the adrenal androgens. Maximal androgen blockade (MAB) aims to block the stimulatory action of this adrenal-derived DHT by adding antiandrogens to surgical or medical castration. Some of the largest and best controlled randomized trials in Europe and the United States have shown statistically better progression-free survival, overall survival, and survival from death by prostate cancer with MAB than with monotherapy with a GnRH agonist or with bilateral orchiectomy. Trial 30853 of the European Organization for Research and Treatment of Cancer (EORTC) compared MAB using a combination of goserelin subcutaneous depot (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) and flutamide with bilateral orchiectomy. Some other published trials did not find the differences revealed by EORTC 30853, however, and so an overview or meta-analysis of trials on the effects of MAB was organized jointly by the American Cancer Society, the Urological Group of the EORTC, and the International Prostate Health Council. Preliminary results on some of the 23 trials included in the meta-analysis showed an advantage of the GnRH agonist therapy in combination with an anti-androgen, particularly in time to progression. If time to progression is viewed as improved quality of life due to the absence of symptoms, a net result in favor of the combination therapy is noted. The MAB trials, using flutamide as the antiandrogen, also showed a small but distinct improvement in survival with the combination treatment. An emphasis on prognostic factors allows treatment decisions to be reached more easily.
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PMID:Role of maximal androgen blockade in advanced prostate cancer. 817 10


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