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)

Sleep-related erections in 5 patients with stage T3N0M0 prostate cancer treated with a new nonsteroidal antiandrogen, Casodex, were evaluated with continuous monitoring of penile tumescence and rigidity on multiple nights. Mean serum luteinizing hormone levels were 7.2 +/- 1.2 IU/l. before therapy and increased to 14 +/- 3.6 IU/l. after 6 months of therapy. Serum testosterone and estradiol levels also increased from a basal level of 5.05 +/- 1.9 ng./ml. and 102 +/- 18 pmol./l., respectively, to 8.04 +/- 1.32 ng./ml. and 175 +/- 20 pmol./l., respectively, after 6 months of therapy. No significant modifications in regard to number of nocturnal penile tumescence episodes, maximum penile circumference and total rigidity time were found before and after therapy. Only 1 patient reported a decrease in sexual drive and libido. All patients presented with stable disease (National Prostatic Cancer Treatment Group criteria) and an unmodified performance status (Eastern Cooperative Oncology Group) after 6 months. Pure antiandrogen therapy did not seem to interfere significantly with the erectile capability of men with prostate cancer.
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PMID:Effect of Casodex on sleep-related erections in patients with advanced prostate cancer. 137 7

Casodex, a pure potent non-steroidal anti-androgen, has been shown in a phase II clinical trial program to be very well tolerated and to have fewer side-effects compared with other anti-androgens. The most commonly reported side-effects (prompted by direct questioning) were breast tenderness (63.4%), breast swelling (52.5%), and hot flashes (23.6%). Gastrointestinal disturbances, hepatic impairment, alcohol intolerance, and problems with light adaptation are not associated with Casodex treatment. In this study, Casodex (50 mg once daily) was evaluated in 267 patients, 130 of whom have received it for more than 1 year. On assessment of best objective response, 55.5% of patients showed partial regression, 15.6% stable disease, 17.1% progression, and 11.8% were not assessable. These results are comparable with other standard hormonal therapies for advanced prostate cancer.
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PMID:Casodex: a pure non-steroidal anti-androgen used as monotherapy in advanced prostate cancer. 157 64

This study evaluates the sleep-related erections in 5 patients with locally advanced prostate cancer (T3NOMO) during 6 months treatment with Casodex by multinight continuous monitoring of penile tumescence and rigidity. Mean serum LH, Testosterone and Estradiol levels shown a no statistically significant increase at the six months control. We found no significant modifications in the number of NPT episodes, maximum penile circumference and rigidity time before and after therapy. Penile arterial flow and neurologic examination were also unmodified. All patients had a stable disease and unchanged performance status after 6 months. This pure antiandrogen in a men with prostate cancer does not seem to interfere with self reported libido and erectile capability.
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PMID:[Monitoring of erection function in patients with prostatic carcinoma treated with Casodex]. 183 Apr 8

Pure anti-androgens have advantages over steroidal anti-androgens of the cyproterone acetate type in the treatment of patients with advanced prostate cancer because they do not have steroidal side effects or such a marked inhibitory effect on libido. In addition, the long half-life of a pure anti-androgen such as Casodex results in maintenance of high serum anti-androgen concentrations, which allays concern over the clinical significance of any small rise in serum testosterone concentrations. The anti-androgen of choice for the treatment of androgen-responsive diseases has yet to be defined. However, this choice should be based on extensive clinical evaluations of a drug as monotherapy. As always, the clinical efficacy and tolerability of the drug will be important factors in determining the anti-androgen of choice; however, favorable pharmacokinetics should be emphasized in the treatment of a disease in which high and sustained concentrations of antagonist must be present to prevent androgenic stimulation. Casodex, a pure anti-androgen with a relatively long half-life, produces objective and subjective responses similar to those of surgical or pharmacologic castration and is well tolerated. Its profile makes it a strong candidate for consideration as the future anti-androgen of choice in the treatment of advanced prostate cancer.
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PMID:Use of the nonsteroidal anti-androgen Casodex in advanced prostatic carcinoma. 199 75

Antiandrogens are effective drugs in the treatment of advanced prostatic cancer. The main problems associated with their use are their short half-lives, leading to fluctuating serum levels, and their non-selectivity, which leads to increases in serum LH and testosterone through centrally-mediated actions. Casodex is a pure, potent antiandrogen which, in pre-clinical studies, has been shown to have a long half-life and a high degree of peripheral selectivity. Casodex is as effective as surgical castration or medical castration with Zoladex in inhibiting the growth of a transplantable Dunning prostate tumor in rats. These properties suggest that Casodex, given once daily, would be an effective and well-tolerated monotherapy for advanced prostatic cancer.
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PMID:Casodex: preclinical studies. 209 8

Recently a new non-steroidal antiandrogen (Casodex) has been shown in animal experiments to possess a potent peripheral antiandrogen effect. In patients with advanced prostatic cancer however, this drug is not peripherally selectively active and blocked central brain androgen-receptors results in a rise of luteinizing hormone (LH) and testosterone (T). We treated 18 advanced prostatic cancer patients with 50 mg Casodex daily for a mean period of 42 weeks. There were no complete objective responses but partial responses were seen in a few patients. In 16 patients there was a greater than 50% reduction of pretreatment PSA levels. Endocrine evaluations showed a significant rise in LH, T and oestradiol (E), reaching peak values within the two first months with subsequent lowering of these levels afterwards but without returning to normal. The general tolerance of the drug was good, gynecomastia being the most frequent side-effect. Libido and potency, when present before start of therapy, were maintained in some patients. We conclude that this compound seems as effective as other antiandrogens, but with improved compliance, and shows less side effects in the management of advanced prostatic cancer.
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PMID:Clinical profile of a new non-steroidal antiandrogen. 212 36

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 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

The population at risk of prostate cancer is on the increase, and so is public awareness of this disease. There has been an unresolved controversy surrounding the benefits of maximal androgen blockade (MAB) as a valid approach to treatment of non-curative prostate cancer since it was first proposed in 1945. How are we to interpret the data on MAB in order to give each patient the best advice on treatment? Studies of MAB using medical castration (luteinizing hormone-releasing hormone [LHRH] analogue plus antiandrogen) vs. LHRH analogues alone are inconclusive when viewed collectively, although the largest showed objective benefits for MAB. The remaining studies have insufficient power to show the expected effect size. Studies of MAB using surgical castration plus antiandrogen vs. surgical castration alone also gave inconsistent results, although a meta-analysis is in favor of MAB on objective criteria of response. Among trials of MAB using an LHRH analogue vs. surgical castration alone, one is positive and the remaining two are neutral for MAB. No study shows MAB to be worse than either medical or surgical castration alone. An overall meta-analysis shows a trend for benefit with MAB but is not statistically significant. The existing data have strongly suggested that there may be a particular benefit for certain subgroups of patients (including those with minimal disease) but numbers studied have been too small to allow valid conclusions. The INT 0105 trial in progress may permit firmer conclusions to be drawn on this and other questions. In the meantime one of the drawbacks to current MAB regimens is the exchange of modest clinical advantages for the side effects of nilutamide and flutamide. Given that the disease is noncurative, improved quality of life is the main goal of therapy, and excellent tolerability of treatment is fundamental to this. In a comparative trial, bicalutamide (Casodex) was more effective than flutamide (each in combination with an LHRH analogue) in terms of time to treatment failure and produced a significantly lower incidence of diarrhoea. In conclusion, the evidence supports early use of adequate hormonal treatment, and this should mean either medical or surgical castration, ideally augmented by an antiandrogen. Tolerability of the antiandrogen is a key consideration in gaining an improvement in quality of life with MAB.
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PMID:Commentary on maximal androgen blockade in prostate cancer: a theory to put into practice? 882 89

Prostate-specific antigen (PSA) has been shown over the past few years to be a useful and sensitive marker for prostate cancer. During Phase III studies of the nonsteroidal antiandrogen, Casodex, in which different doses were compared with castration (either surgical or medical), serum PSA was measured on a regular basis. Attention was focused on the change in serum PSA from baseline after 3 months Casodex treatment and also on the number of patients receiving Casodex whose PSA returned to the normal range. Data from trials comparing Casodex, 50 mg/day, with castration showed a clear shortfall for Casodex compared with castration, in terms of percentage fall in PSA at 3 months, and also in the number of patients whose PSA fell into the normal range after 3 months. Subsequent analysis showed, however, that the PSA level was related to outcome in terms of time to progression. These data allowed the use of PSA to determine dose selection in a subsequent trial comparing Casodex, 100 mg/day or 150 mg/day, with castration. At the time of dose selection, changes in PSA showed a statistically significant difference between Casodex, 100 mg/day, and castration, but no significant difference between Casodex, 150 mg/day, and castration, either for the change in PSA at 3 months or for the proportion of patients whose PSA had fallen into the normal range. The idea that serum PSA levels can predict outcome in prostate cancer and that they are correlated with other measures of outcome, such as time to progression, is supported by these data. A decrease in PSA is not a true surrogate endpoint in that it cannot predict the outcome for an individual patient with complete accuracy, but it does correlate well with other measures of outcome, such as time to progression, for patient populations.
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PMID:Role of prostate-specific antigen as a predictor of outcome in prostate cancer. 751 30


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