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 compared the efficacy and safety of the gonadotropin-releasing hormone analogue, leuprolide (1 mg subcutaneously daily), with diethylstilbestrol (DES, 3 mg by mouth daily) in patients with prostate cancer and distant metastases (Stage D2) who had not previously received systemic treatment. Initial therapy (leuprolide or DES) was continued for as long as an objective response was noted; cross-over to the alternative arm occurred at the time of disease progression or intolerable adverse reactions. Ninety-eight patients were randomly assigned to leuprolide, and 101 to DES. Suppression of testosterone and dihydrotestosterone and decreases in acid phosphatase were comparable in the two groups. Patients receiving DES experienced more frequent painful gynecomastia (P less than 0.00001), nausea and vomiting (P = 0.02), edema (P = 0.008), and thromboembolism (P = 0.065) than those receiving leuprolide. The leuprolide group reported more "hot flashes" (P = 0.00001). Overall, 86 per cent of the leuprolide group had an objective response (complete response, 1 per cent; partial response, 37 per cent; stable disease, 48 per cent), as compared with 85 per cent of the DES group (complete, 2 per cent; partial, 44 per cent; stable, 39 per cent). Actual survival rates at one year were 87 per cent for the leuprolide group and 78 per cent for the DES group (P = 0.17). We conclude that leuprolide offers an important alternative treatment that is therapeutically equivalent to and causes fewer side effects than DES for the initial systemic management of metastatic prostate cancer.
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PMID:Leuprolide versus diethylstilbestrol for metastatic prostate cancer. 643

Two parallel prospective randomized studies have been undertaken by the EORTC Urological Group in previously untreated patients with prostatic cancer in order to compare low dose Stilboestrol versus Cyproterone acetate versus Medroxyprogesterone acetate in the first trial, and Stilboestrol versus Estracyt in the second trial. Although the follow up is still short, no superiority of the other drugs over Stilboestrol had appeared so far with regard to either objective response or significant side effects apart from gynaecomastia. In the third trial, patients with advanced disease no longer responsive to hormonal treatment were randomized to either Adriamycin or Procarbazine. Toxicity and early death were particularly frequent in Procarbazine treated patients, whereas most patients progressed in both treatment groups.
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PMID:EORTC protocols in prostatic cancer. An interim report. 693 20

Benign breast disease (BBD), of which fibrocystic disease (FCD) is the most common, results from an imbalance in estrogen-progestogen ratios or inappropriate target gland response to changing tides of hormonal stimulation. Histologically, FCD may present as simple cystic glandular hyperplasia, adenosis, chronic cystic mastitis with apocrine metaplasia, and ductal papillomatosis. Fibroadenoma, a pseudoencapsulated tumor, is another variant. Experimental animal data yield some clues as to the etiology of FCD, but extrapolation to the human may be inappropriate. The anovulatory female rarely develops severe FCD, as manifested by marked pain and lumpiness. Oral contraceptives (OCs) reduce the incidence of FCD and the frequency of mammary cancer in comparison with controls. The administration of methyltestosterone, and at times testosterone, to males has resulted in multiple soreness and gynecomastia. Cancer of the breast has occurred in 2 male transvestites who had been on estrogens. The development of mammary cancer in men on stilbestrol therapy for prostatic cancer has recently been challenged. 1 in 11 women in the U.S. will develop breast cancer in her lifetime. Warren has claimed that malignancy was 4.5 times greater in women who had been biopsied for FCD than in normal female population. Cole and MacMahon reviewed the world literature and found the presence of FCD increased the risk of cancer by 2.64 times. FCD is an exaggeration of the normal tissue response of the breast resulting from the ebb and flow of ovarian hormones. FCD is characterized by pain and tenderness, most marked in the premenstrual period but later may continue throughout the cycle. The lumpiness or nodularity may be localized or generalized, unilateral or bilateral. Reported surveys showing that oral contraceptives (OCs) lessen the incidence of FCD suggest that hormonal manipulation can effectively reduce the frequency of this disease, and, possibly in turn, the incidence of mammary cancer. Cystic masses should be aspirated and the contents examined for cytologic atypia. It is important to find those women who are at greater risk of developing mammary cancer because of florid fibrocystic disease. FCD should be medically managed unless a dominant lump develops, in which case a biopsy should be performed. The use of a newsteroidal agent, danazol, on a 3-6 month trial of 100-400 mg/day will eliminate pain and nodosities in some 69% of women and in another 30% the signs and symptoms will be diminished.
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PMID:Fibrocystic disease of the breast. 710 13

In an attempt to maximize the quality of life of advanced prostate cancer patients on prolonged total androgen ablation and to minimize side effects, we have devised a strategy of 'sequential androgen blockade'. Animal studies have demonstrated that the combination of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide was as effective as a luteinizing hormone-releasing hormone analog and flutamide in inhibiting the growth of the prostate. In a pilot trial, 10 potent patients with clinical stage C and D1 prostate cancer were given the combination of finasteride (5 mg b.i.d.) and flutamide (125-250 mg t.i.d.). Eight of ten men remained potent. At 3 months the mean prostate-specific antigen level of all patients was 3.8 ng/ml (34 ng/ml prior to therapy). In all patients serum testosterone increased and those with the highest increase demonstrated gynecomastia. The combination was easily tolerable and side effects were few. This treatment regime appears to offer the benefits of total androgen blockade, is less expensive and has fewer side effects. Further trials are warranted.
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PMID:Treatment of advanced prostate cancer with the combination of finasteride plus flutamide: early results. 750 29

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

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

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

Male breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men, but the male/female ratio is higher among black than among white populations. This effect can be seen in US cancer registries and even more markedly in African data. A positive correlation exists on a population scale between male breast cancer and prostate cancer. Seven case-control studies of male breast cancer are available, and a pooled analysis was conducted of the most commonly suspected risk factors. Male breast cancer appears to be associated with marital status: Mantel-Haenszel exposure odds ratio (EOR) for never married = 1.6; 95% confidence limits (CL) = 1.1, 2.3, religion (EOR for being Jewish = 2.1; 95% CL = 1.4, 3.2), previous breast pathology (EOR for positive history of benign breast disease = 2.7; 95% CL = 1.7, 4.2), gynaecomastia (EOR for positive history = 6.2, 95% CL = 3.4, 11.4), previous testicular pathology (EOR for positive history = 2.2; 95% CL = 1.5, 3.3), previous liver diseases (EOR for positive history = 1.6; 95% CL = 1.0, 2.4) and family history of breast cancer (EOR for first-degree relative with breast cancer = 2.5; 95% CL = 1.7, 3.7). No association is found with smoking history. Other potential risk factors such as reproductive history, education, occupation, anthropometric variables, association with various diseases, and specific exposures such as drug use, were not systematically evaluated in all studies and provide sometimes contradictory results, possibly due to small numbers of exposed subjects. Overall, the analytical epidemiology of male breast cancer presents similarities with the epidemiology of female breast cancer, with a potential role of factors related to hormonal status, relative hyperoestrogeny in men being potentially linked to increased risk of disease. Genetics may also play a role, with high risk linked to a familial history of breast cancer, and with a major risk in patients with Klinefelter's syndrome.
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PMID:Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. 843 28

Low levels of testicular estrogen synthesis have been reported in a number of species, but the cellular localization has not been unequivocally established. To study aromatase in the human testis, we have combined immunocytochemistry with direct measurement of enzyme activity in the testicular 6 microns cryosections. Thus, the functionality of the immunoreaction and its sensitivity can be assessed in quantitative terms. Testes were obtained from immediate autopsy from men aged 18-53 years, from surgery from two patients with prostatic cancer (67 and 74 years) and from two normal children aged 8 months and 3 years at autopsy. Benign testicular sex cord tumors were also examined from two unrelated patients aged 5 and 8 years with gynecomastia and diagnosed with Peutz-Jeghers syndrome. Our results consistently showed low to moderate staining intensity of immunoreactive aromatase in comparison to that of normal human placental cryosections. Immunoreactive aromatase was only present in the interstitial Leydig cells and absent from the Sertoli cells of all normal adult testes showing spermatogenesis. Aromatase activity correlated well with the intensity of the immunostain. However, there was no obvious relationship between the level of aromatase activity and increasing age. Generally higher levels were present in testes of young men (18-22 years). No immunostain in any cell type was detected in one 33-year-old patient with testicular cancer. In the testes of the two normal prepubertal boys, no immunostaining was observed. However, intensely stained Sertoli cells as well as high aromatase activity were observed in the testicular tumors of the patients with Peutz-Jeghers syndrome. Our results suggest that Leydig cells are the source of aromatase in normal men but that Sertoli cells may express this enzyme under abnormal conditions. The combined methods for measuring enzyme activity and immunoreactive aromatase are suitable for application to tissues expressing low levels of aromatase.
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PMID:Aromatase in the human testis. 847 68


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