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)

The trial drug was ICI 118.630 (Zoladex). Inclusion criteria were histologically confirmed advanced prostate cancer (T greater than 2 or N+ or M+), life expectancy greater than 3 months, and no previous radiotherapy, orchiectomy, or chemotherapy. Treatment started in November 1984; 30 patients were recruited. The period of treatment ranged from 6 to 144 weeks (median of 59.5 weeks). One patient died after 6 weeks of rapidly progressive renal failure. Data were updated to the end of August 1987. The mean age was 67.9 years (53-83 years). Subjective response was evaluated by a mean symptoms score (using daytime micturition, nocturia, dysuria, hesitancy, and flow) and a score of three different items: patients' activity, bone pain, and use of analgesics. Only 7.1% of the patients showed a permanent positive response. Four different objective responses (complete, partial, stable disease, and progression) were possible after evaluating the T category, tumor dimensions, metastases, and prostatic acid phosphatase. Testosterone (T) and plasmatic LH levels rose after administration: T dropped below the castration level (1 ng/ml) within a few days and remained constantly low. The rate of progressive disease was 27.6%; disease control was possible in 72.4% of the patients (PR or SD).
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PMID:LH-RH analogue treatment for advanced prostate cancer. 297 66

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

A radioimmunoassay is described for D-Ser (tBu)6 AZA Gly10 GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With 125I-118630 as the label, and an anti-GnRH serum, the specificity of the assay is directed to the N-terminal end of the peptide, and putative degradation products have less than 6% cross-reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 micrograms, has a half-time of disappearance from the serum of 4.9 +/- 0.4 h and a volume of distribution of 13.7 +/- 0.8 litres. Continuous subcutaneous infusion of 120 micrograms 118630/d gave stable serum concentrations of between 2-3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the "peak and trough' pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3.6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6-8 ng/ml 15 d after the implant and fell to less than 1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3.6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long-acting formulations, but also for correlation of serum peptide concentrations with pituitary gonadotroph desensitization.
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PMID:A radioimmunoassay for GnRH agonist analogue in serum of patients with prostate cancer treated with D-Ser (tBu)6 AZA Gly10 GnRH. 315 12

Patients with advanced breast cancer or advanced prostate cancer have been treated with an LH-RH-agonist ICI 118630. A chemical castration-like response has been achieved in all patients and is associated with clinical remission of the disease.
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PMID:Influence of LH-RH agonists on the growth and hormonal environment of breast and prostate cancer. 316 43

The influence of the LH-RH agonist ICI 118630 on circulating levels of the pituitary gonadotrophins LH and FSH and the gonadal steroids oestradiol, progesterone, 17-hydroxyprogesterone and testosterone has been studied in phase I clinical trials of the drug in patients with advanced breast or prostate cancer. ICI 118630 initially stimulated plasma levels of LH and FSH. On continued treatment however, the drug reversed this response and produced a rapid decline in plasma testosterone and progesterone in male and female patients respectively. Plasma oestradiol concentrations equivalent to those seen in oophorectomised or postmenopausal women were eventually produced in all 5 female patients treated with ICI 118630. In one patient however persistent follicular activity occurred until her third menstrual cycle. No appreciable side effects of the drug were observed. These data indicate that ICI 118630 initiates a castration-like endocrine response and has potential in the treatment of hormone dependent tumours of the breast and prostate.
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PMID:Therapeutic significance and the mechanism of action of the LH-RH agonist ICI 118630 in breast and prostate cancer. 623 16

Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics.
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PMID:Experience with an LHRH analogue in the management of relapsed progressive prostatic cancer. 624 22

We report that growth of LNCaP human prostate cancer cells is significantly stimulated (up to 120% above control) by physiological estradiol (E2) concentrations. This growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone, as also reported by others. This paper presents novel illustrative evidence for estrogen-binding proteins and messenger RNA transcripts in LNCaP cells. In fact, 1) the reverse transcriptase-polymerase chain reaction system documented normal messenger RNA for estrogen receptors (ER); 2) the radioligand binding assay allowed the detection of high affinity, reduced capacity binding sites in both soluble and nuclear cell fractions; and 3) the immunocytochemical analysis showed a consistently intensive staining for both ER and progesterone receptors. Compared to other human estrogen-responsive mammary cancer cells, MCF7 and ZR75-1, ER expression in LNCaP cells was not significantly lower, as shown by levels of the ER transcripts, number of sites per cell, or femtomoles per mg DNA as well as the percentage and intensity of immunocytochemical staining. A relative estimate of ER expression obtained by matching LNCaP with another human prostate cancer cell line, PC3, always displayed significantly and consistently higher levels in LNCaP cells. The detection of relatively high type I ER content in either cell compartment of LNCaP cells was paralleled by a highly intensive staining for progesterone receptors. In addition, evidence that the synthetic androgen R1881 did not compete for type I binding of E2 and that any E2-induced growth was completely reversed by the pure antiestrogen ICI-182,780, but unaffected by the antiandrogen Casodex, clearly suggests that the biological response of LNCaP cells to E2 is mediated via its own receptor.
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PMID:Growth of LNCaP human prostate cancer cells is stimulated by estradiol via its own receptor. 753 68

Over 3,000 men, the majority of whom were patients with prostate cancer, were treated with Casodex (ICI 176,334), an oral anti-androgen, at doses ranging from 10 to 200 mg daily, corresponding to a total exposure to the drug of over 1,500 patient-years. Over this period, the tolerability of Casodex and its effect on quality of life were closely studied. Information on tolerability is presented from three large randomized trials of Casodex, 50 mg/day, in patients with prostate cancer, two large randomized trials of Casodex, 150 mg/day, in patients with prostate cancer and three double-blind, placebo-controlled trials of Casodex, 50 mg/day, in patients with benign prostatic hyperplasia (BPH). Information on quality of life and assessment of sexual functioning is presented from the trials using Casodex, 50 mg/day, for both prostate cancer and BPH. The most commonly reported adverse events were those that would be expected with an anti-androgen (i.e. breast tenderness, gynaecomastia and hot flushes). Overall, Casodex was well tolerated; there were no reports of light/dark adaptation problems or pulmonary fibrosis, and only one case of alcohol intolerance, which was not considered by the investigator to be treatment related. Only 0.3% of patients in the whole trial programme had to be withdrawn because of changes in liver function, and there were no clinically significant changes in mean liver function tests. Although there were no consistent differences between treatments for other aspects of quality of life, there was evidence of benefit from treatment with Casodex in maintaining both sexual interest and functioning.
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PMID:Tolerability and quality of life aspects with the anti-androgen Casodex (ICI 176,334) as monotherapy for prostate cancer. International Casodex Investigators. 753 64

There is convincing evidence that a reduced expression of the E-cadherin cell-cell adhesion molecule associates with low tumor grade and poor prognosis in prostate cancer patients. However, little is known on how E-cadherin levels are regulated in human prostate cancer cells. We have inspected the effect of both androgens and estrogen on the expression of E-cadherin in the hormone-responsive LNCaP prostate tumor cell line, which is endowed with both androgen and estrogen receptors. Using both Dot Blot analysis and immunocytochemistry we have observed that either steroid significantly increased E-cadherin levels in these cells; this effect was not reversed by the simultaneous addition of the relevant antagonist, hydroxyflutamide or ICI-182,780.
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PMID:Sex steroids up-regulate E-cadherin expression in hormone-responsive LNCaP human prostate cancer cells. 762 77


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