Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An estimated 32,000 American men will die of prostate cancer this year. Local prostate cancer may be successfully treated by radical prostatectomy or radiotherapy. Advanced cases may necessitate the use of hormonal ablation with bilateral orchiectomy, an approach that is regarded as the gold standard of therapy but not always the preferred treatment of patients. Oestrogen therapy is an alternative but is associated with side effects, such as hot flushes and gynaecomastia, which frequently lead to treatment cessation. Luteinising hormone-releasing hormone (LHRH) analogues work by initially producing a surge of androgen, followed by a down-regulation in hormone production to effect a medical castration. Various groups have studied the effects of androgen blockade administered as monotherapy and as combination therapy (LHRH analogue plus antiandrogen). The National Cancer Institute intergroup protocol 0036, which is the largest cooperative study to date of patients with advanced prostatic cancer, showed that combination therapy with leuprolide and flutamide offered greater benefit in both time to disease progression and median survival while circumventing tumour flare and its associated symptoms. Thus, combination therapy for total androgen ablation may become the new treatment standard for advanced prostatic cancer, pending further studies in the efficacy and cost-effectiveness of all available treatments.
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PMID:Challenges in the management of prostate cancer. 146 76

Cyproterone acetate is a progestational antiandrogen with potent antigonadotropic activity that results in rapid suppression of serum testosterone. Used as a single agent, cyproterone acetate yields a total androgen blockade. It may be combined with low-dose diethylstilbestrol, orchiectomy, or LHRH agonists to improve, in theory, the results of such therapy. In clinical testing, cyproterone acetate has proved equivalent to diethylstilbestrol with markedly less toxicity. It is useful in conjunction with LHRH agonists, either transiently to block the flare phenomenon, or continuously to block peripheral androgen receptors; the necessity for this latter action has not yet been proved. Cyproterone acetate may afford transient objective improvement in patients not responding to other forms of hormone deprivation. Experience in this role is limited. The drug may be used to suppress the hot flushes associated with orchiectomy or LHRH agonist therapy. Cyproterone acetate induces local tumor regression; owing to its reversible effects, it is useful as neoadjuvant or adjuvant androgen withdrawal therapy in patients with lower-stage disease undergoing radical surgery or radiotherapy. Adverse effects are mostly those related to hormone withdrawal, namely, impotence, infertility, and lassitude. Gynecomastia and breast tenderness occur in less than 18% and cardiovascular complications in approximately 10% of treated men.
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PMID:Use of cyproterone acetate in prostate cancer. 182 43

Cyproterone acetate (CPA) has been discovered more than 25 years ago and it was the first antiandrogen suitable for clinical use. CPA inhibits the action of endogenous and exogenous androgens at all androgen target organs; these include the prostate, seminal vesicles, testes, and the vas deferens. However, this antiandrogen also antagonizes less sex-specific effects of androgens, for example ossification of the epiphyseal cartilage, sebaceous gland function and skin thickness. Indications for CPA: Prostate cancer, androgen induced disorders of the skin (acne, seborrhoea, hirsutism, alopecia), precocious puberty and sexual disorders in men. Concerning sexual deviations clinical trials started in 1966. CPA leads to loss of libido and the ability to achieve erection, followed by the inability to achieve orgasm, after about 14 days of treatment (100-200 mg daily orally or 300 mg weekly i.m.). These effects are reversed in the same order as the onset. About 75 to 80% of patients respond to this therapy. CPA is generally well tolerated. Tiredness, lack of drive, listlessness and depressive moods have been reported as non-specific side-effects. Slight gynecomastia occurs in about 20% of patients. There are no good alternatives in this indication. Pure antiandrogens are unsuitable, because these are unable to inhibit libido sufficiently. Tranquilizers are not very effective, high doses of estrogens are associated with severe (cardiovascular) side effects. Orchidectomy is an irreversible intervention, LHRH analogues are associated with hot flushes and the initial increase in testosterone (flare phenomenon).
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PMID:Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience. 183 80

In a randomized, prospective trial, 199 previously untreated patients with Stage D2 prostatic cancer were treated with 3 mg/day diethylstilbestrol (DES) or 1 mg/day leuprolide acetate, a luteinizing hormone releasing hormone analog. Both DES and leuprolide suppressed testosterone to the desired castrate levels. Objective measures of disease, such as acid phosphatase levels, and subjective measures, such as bone pain, performance status, and mobility, showed similar decreases in both groups. No progression of disease was seen in 86 per cent of the leuprolide-treated group, compared with 85 per cent of the DES-treated group. The time to disease progression, development of adverse reaction requiring discontinuation of treatment, or death was identical for the two groups. Hot flashes were more common with leuprolide than with DES. Gynecomastia and breast tenderness, nausea and vomiting, and peripheral edema occurred more often in the DES group. Of those taking DES, 13 per cent discontinued treatment because of side effects, compared with 3 per cent of those taking leuprolide.
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PMID:Leuprolide versus diethylstilbestrol for previously untreated stage D2 prostate cancer. Results of a prospectively randomized trial. 307 35

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

The efficacy and tolerability of Casodex, a new non-steroidal antiandrogen, were studied in 267 patients with advanced prostate cancer. All patients received Casodex, 50 mg daily, as monotherapy. The objective response rate was 55.5% and the subjective response rate was 56.1%. The most common adverse events were the expected pharmacological effects of breast tenderness, gynecomastia and hot flushes. No other adverse events were reported in more than 5% of patients. There was minimal occurrence of impotence, loss of libido and diarrhea. The results show that Casodex 50 mg is effective and well tolerated in the treatment of advanced prostate cancer.
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PMID:Efficacy and tolerability of Casodex in patients with advanced prostate cancer. International Casodex Study Group. 757 54

Epidemiological evidence, including the greater incidence of female patients, a positive association with pregnancy, and a positive association with breast cancer suggested a role for female sex hormones (and hormonal modulation) in regulating the growth of meningioma. The detection of hormone receptors on meningioma specimens provided a mechanism for this effect. However, unlike breast cancer, progesterone receptors (not oestrogen receptors) predominate in meningioma. Clinical trials with anti-oestrogens have shown little effect while trials with progesterone agonists have shown no effect or possible stimulation of meningioma growth. Three trials have now indicated an inhibitory activity of the antiprogestational agent mifepristone. In the largest of these trials, 28 patients received daily oral mifepristone for up to 62 months with a suggestion of response in eight patients. Long-term therapy has been well tolerated. Adverse events include fatigue, hot flushes, gynaecomastia/breast tenderness, skin rash, cessation of menses and decrease in libido. Increases in cortisol and thyroid-stimulating hormone are the most striking endocrine changes. A randomized double-blind placebo-controlled phase III trial is underway to confirm the activity of mifepristone in unresectable meningioma.
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PMID:Role of antiprogestational therapy for meningiomas. 796 66

Androcur 50 was administered as monotherapy (n = 73) or as combined therapy with LH-RH agonists (n = 130) in 203 patients during a 6 month period. Eighty two patients had a local invasive disease, 119 had metastatic disease and 2 had a tumor confined to the prostate. Quality of life could be evaluated in 164 patients considered as valid cases for efficacy analysis. General well being improved in 41% of the patients, appetite was better in 34% of the patients and weight increased in 36%. Pain due to metastatic disease decreased or stabilised in 96% of the patients. Of the 203 patients, 8 patients had objective metastatic progression which led to death in one patient. The incidence of side effects observed in all 203 is as follows: 9% gynaecomastia, 6.5% gastro-intestinal disorders. Hot flushes were reported in 2% of the patients in the monotherapy and in 13% of the patients in the combined treatment. This open not controlled trial shows that the use of Androcur 50 in monotherapy or in combined treatment is an effective drug for prostatic carcinoma, improves quality of life and is generally well tolerated.
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PMID:Androcur 50 in the treatment of prostatic carcinoma. Belgian multicentric study with the participation of 30 urologists. 819 33

Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.
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PMID:Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. 836 20

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.
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PMID:[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer]. 871 91


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