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)

Casodex (Bicalutamide, ICI 176,334) is a potent, non-steroidal, selective anti-androgen with a long half-life allowing once-daily oral administration. In this randomised, open, multicentre study, Casodex 50 mg monotherapy was compared with castration (medical, using goserelin acetate, [Zoladex], or surgical) in 245 patients with advanced prostate cancer. Primary end-points were time to treatment failure, time to objective progression and survival. Subjective responses, quality of life and tolerability were also evaluated. There was no significant difference between the groups in terms of objective progression or subjective responses. Treatment failed in 59 of 119 patients (50%) randomised to Casodex and in 61 of 126 patients (48%) randomised to castration (no statistically significant difference). An updated analysis showed that survival was similar in the two groups. Casodex was well tolerated with a low incidence of diarrhoea and sexual dysfunction. On the basis of this study, Casodex monotherapy is an effective alternative to castration in the treatment of metastatic prostate cancer.
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PMID:A randomised comparison of monotherapy with Casodex 50 mg daily and castration in the treatment of metastatic prostate carcinoma. Casodex Study Group. 853 75

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.
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PMID:[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer]. 871 92

The potential for hepatic enzyme induction by bicalutamide ('Casodex') was assessed in an open study in prostate cancer patients. A single, oral dose of antipyrine 1000 mg was given before and after 12 weeks' bicalutamide therapy [once daily 50 mg (n = 7) or 150 mg (n = 11)] and its pharmacokinetics and metabolism were determined. Plasma or saliva samples were taken for the measurement of antipyrine concentration. Urine samples were assayed for antipyrine and its three major metabolites. With bicalutamide 50 mg, plasma antipyrine concentrations were maximal between 2 and 4 h after administration, declined in a log-linear manner and were unaffected by bicalutamide therapy; with bicalutamide 150 mg, saliva antipyrine concentrations were maximal between 2 and 4 h, declined in a log-linear manner, and were also unaffected by bicalutamide therapy. Antipyrine half-life was 16.3% shorter after bicalutamide 50 mg (p < 0.05); a small decrease (13.5%) in half-life after bicalutamide 150 mg was not statistically significant. A small reduction (18.6%, p < 0.05) in the AUCinfinity for antipyrine was noted after bicalutamide 150 mg. A statistically significant reduction in antipyrine recovery was seen with the lower bicalutamide dose (23.7%, p < 0.05). The statistically significant changes were small in absolute terms and showed no dose-response relationship. Bicalutamide does not significantly induce the hepatic enzymes responsible for antipyrine metabolism and has no obvious potential for producing clinically significant drug interactions due to enzyme induction.
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PMID:Absence of hepatic enzyme induction in prostate cancer patients receiving 'Casodex' (bicalutamide). 874 99

Endocrine therapy for prostate cancer has been changing rapidly. While LH-RH agonists have been popularly used in medication, their long-acting sustained release formulation is about to be introduced to clinics in Japan. LH-RH antagonists, which have not attracted much attention of clinicians because of adverse reactions, are also going to be put into practical use in the near future. Bicalutamide, which is considered to have greater usefulness than other anti-androgens, is now under regulatory review by the authorities for approval. In addition, a broader range of endocrine therapies is being studied for treatment of prostate cancer. In terms of treatment methods, a number of attempts are made in selection of subject patients, treatment timing, combination treatment and so on.
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PMID:[Endocrine therapy for prostate cancer in the future]. 961 19

Mutations in the androgen receptor (AR), that alter steroid hormone specificity have been identified in a series of androgen-independent prostate cancers. To address the functional properties of these mutant ARs that may have contributed to their selection in vivo, responses to a series of steroid hormones and antiandrogens were assessed. CV-1 cells were cotransfected with wild-type or mutant ARs and a luciferase reporter plasmid regulated by an androgen-responsive element. Dose-response curves were analyzed for 5alpha-dihydrotestosterone, the most active androgen in normal prostate, and androstenedione, a major androgen derived from the adrenals. Although the mutant ARs responded to both of these steroids, the responses were equivalent to or less than the wild-type AR. In contrast, responses to flutamide, a competitive antagonist of the wild-type AR, were markedly increased by three of the mutations. Similar responses were observed with a second antiandrogen, nilutamide. Bicalutamide, another antiandrogen related to flutamide, remained an antagonist for these mutant ARs. Finally, flutamide was observed to be a weak partial agonist of the wild-type AR in this system. These results indicate that flutamide used in conjunction with androgen ablation therapy for prostate cancer may select for tumor cells with flutamide-inducible ARs.
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PMID:Functional characterization of mutant androgen receptors from androgen-independent prostate cancer. 981 22

Bicalutamide (Casodex) is a new antiandrogen, so far approved for the treatment of prostate cancer in combinations with a GnRH agonist. Results from large, well controlled studies show that monotherapy with bicalutamide is an interesting alternative to surgical or medical castration for patients with advanced prostate cancer. The efficacy generally appears to be similar to that of castration, but without the well known side effects of castration such as hot flushes, reduced sexual interest and functioning, and reduced physical capacity. Bicalutamide is well tolerated, but some patients will experience gynaecomastia and/or breast tenderness, and they should be informed about this before treatment is started. Monotherapy with bicalutamide is an attractive first line treatment for these patients in order to maintain optimal quality of life for as long as possible. Studies show that many patients will respond to second line treatment with castration if bicalutamide has failed.
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PMID:[Monotherapy with antiandrogens for prostatic cancer]. 1035 54

Bicalutamide (Casodex) has been approved as a new option for the treatment of prostate cancer. It is a new non-steroidal anti-androgen synthesized by the British company Zeneca. In pharmacological studies using rats and other subjects, the product showed excellent affinity with androgen receptors and was found to be anti-androgen active and effective against tumors, and so clinical trials have begun. Approval has been obtained in approximately 70 countries, including the United Kingdom, the United States and Germany. Anti-androgens are used extensively in combination with LHRH analogs or surgical castration (MAB therapy) in the treatment of prostate cancer. Overseas, encouraging results have been obtained from comparative trials using bicalutamide or flutamide in MAB therapy. Bicalutamide is expected to be highly effective. Moreover, it can be administered in a once-daily dose, which is expected to improve patient compliance. In a late Phase II study in Japan, a response rate as high as 64.4% was achieved when bicalutamide was administered alone. The potential for bicalutamide to be used alone is important because of the growing emphasis on patient quality of life and sexual function in prostate cancer therapy.
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PMID:[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer--basic clinical aspects]. 1043 91

Advanced prostate cancer is treated by androgen ablation and/or androgen receptor (AR) antagonists. In order to investigate the mechanisms relevant to the development of therapy-resistant tumours, we established a new tumour model which closely resembles the situation in patients who receive androgen ablation therapy. Androgen-sensitive LNCaP cells were kept in androgen-depleted medium for 87 passages. The new LNCaP cell subline established in this manner, LNCaP-abl, displayed a hypersensitive biphasic proliferative response to androgen until passage 75. Maximal proliferation of LNCaP-abl cells was achieved at 0.001 nM of the synthetic androgen methyltrienolone (R1881), whereas 0.01 nM of this compound induced the same effect in parental cells. At later passages (> 75), androgen exerted an inhibitory effect on growth of LNCaP-abl cells. The non-steroidal anti-androgen bicalutamide stimulated proliferation of LNCaP-abl cells. AR protein expression in LNCaP-abl cells increased approximately fourfold. The basal AR transcriptional activity was 30-fold higher in LNCaP-abl than in LNCaP cells. R1881 stimulated reporter gene activity in LNCaP-abl cells even at 0.01 nM, whereas 0.1 nM of R1881 was needed for induction of the same level of reporter gene activity in LNCaP cells. Bicalutamide that acts as a pure antagonist in parental LNCaP cells showed agonistic effects on AR transactivation activity in LNCaP-abl cells and was not able to block the effects of androgen in these cells. The non-steroidal AR blocker hydroxyflutamide exerted stimulatory effects on AR activity in both LNCaP and LNCaP-abl cells; however, the induction of reporter gene activity by hydroxyflutamide was 2.4- to 4-fold higher in the LNCaP-abl subline. The changes in AR activity were associated neither with a new alteration in AR cDNA sequence nor with amplification of the AR gene. Growth of LNCaP-abl xenografts in nude mice was stimulated by bicalutamide and repressed by testosterone. In conclusion, our results show for the first time that the nonsteroidal anti-androgen bicalutamide acquires agonistic properties during long-term androgen ablation. These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention.
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PMID:Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system. 1049 49

There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme.
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PMID:A review of studies of hormonal adjuvant therapy in prostate cancer. 1052 61

Recent interest has focused on the use of hormone therapy in prostate cancer for both the management of patients with non-metastatic disease and as a neoadjuvant or adjuvant to curative therapies. This has resulted in patients with fewer symptoms being treated for longer periods of time. Endocrine treatments for prostate cancer, such as castration, combined androgen blockade and non-steroidal antiandrogen monotherapy, have shown similar results in terms of time to progression and survival. The main difference between these treatments is their impact on patients' quality of life. Instruments for measuring health-related quality of life should assess both overall and disease-specific quality of life. Data from two large studies of bicalutamide monotherapy show that this non-steroidal antiandrogen is associated with significant health-related quality of life advantages in the treatment of patients with locally advanced (M0) disease compared with castration, suggesting that this treatment may benefit patients with early disease. Bicalutamide was favoured in 8 out of 9 evaluable quality of life dimensions, and this was statistically significant for sexual interest and physical capacity. Endocrine treatments with minimal adverse effects on quality of life will be increasingly favoured for patients with non-metastatic disease who are being treated for longer periods of time.
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PMID:Quality of life issues relating to endocrine treatment options. 1052 62


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