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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1,125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1,125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.
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PMID:[Clinical evaluation of flutamide, a pure antiandrogen, in prostatic cancer phase II dose-finding study]. 850 39

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

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

Improvement of quality of life (QoL) has become a major endpoint in clinical trials of patients with prostate cancer. However, there still exist considerable methodological problems regarding the development of optimal instruments and methods for presenting the results. Within the European Organisation for the Research and Treatment of Cancer (EORTC) a core questionnaire is generally used for QoL evaluation, combined with a treatment- and disease-specific module. So far, no official EORTC prostate cancer module has been developed. Previous and ongoing trials in prostate cancer have addressed the following issues: for localised prostate cancer, micturition and sexuality, and for metastatic prostate cancer, bone pain, micturition, sexuality, vitality, hot flushes and gynaecomastia. The future challenge is to incorporate QoL results into the overall evaluation of treatment in combination with survival results and economical considerations.
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PMID:Quality of life in prostate cancer: what are the issues and how are they measured? 871 74

Palliation is the principal aim of treatment for patients with advanced prostate cancer. In a strict sense, "palliation" means reduction of existing symptoms, but in clinical practice a further goal is to prolong the symptom-free interval in asymptomatic patients and to prevent distressing problems, such as pain and fatigue, with the overall aim of improving quality of life. In patients with advanced prostate cancer, quality of life parameters represent an important endpoint in clinical routine and in clinical trials. Evaluation of quality of life issues also provides independent prognostic information. A feasible approach for regular quality of life assessment is the use of a questionnaire developed for cancer patients together with psychometrically tested disease-specific and treatment-specific modules designed to evaluate the various factors, such as micturition, sexuality, vitality, and intestinal problems for localized prostate cancer, and bone pain, micturition, sexuality, hot flashes, gynecomastia, and gastrointestinal problems for metastatic prostate cancer.
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PMID:Quality of life in advanced prostate cancer. 899 83

Ketoconazole has been used with success to treat disseminated intravascular coagulation and acute spinal cord compression syndromes associated with metastatic prostatic adenocarcinoma. It effects prompt, reversible medical castration, making it especially useful as empiric therapy when histologic diagnosis is delayed but prostate cancer is suspected. Side effects are usually limited to asthenia, nausea, diarrhea, and gynecomastia, but a theoretical risk of adrenal suppression exists. We report a case of fulminant adrenal crisis precipitated by ketoconazole given on a 6-hour dosing schedule in a patient with nerve root compression secondary to prostatic metastases. Through a review of the literature, we attempt to provide a better understanding of the use and potential dangers associated with ketoconazole therapy.
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PMID:Ketoconazole-induced adrenal crisis in a patient with metastatic prostatic adenocarcinoma: case report and review of the literature. 914 92

Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or 'pure' antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have 'learned' to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens, bicalutamide offers some advantages over flutamide as it possesses a much longer half-life, allowing a once daily regimen, and has advantages over nilutamide in terms of fewer adverse effects.
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PMID:Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer. 959 22

Over the past 20 years therapeutic options for prostate cancer have increased. Nevertheless, there may still be a role for long-established treatments such as orchidectomy and oestrogens. Orchidectomy is a simple surgical procedure, and patient survival is comparable with other treatments involving androgen ablation. However, loss of libido and sexual function is an expected outcome and hot flushes occur in about 50% of patients. Osteoporosis, loss of muscle mass, and the psychological impact associated with orchidectomy are of concern, particularly with increasing treatment periods. Nevertheless, orchidectomy is indicated when an immediate reduction of testosterone levels is required, or the patient does not comply with other treatments or objects to the cost of medical therapy. Oestrogen therapy may be superior to castration in terms of efficacy, but orally administered oestrogens are associated with gynaecomastia, loss of sexual function and unacceptable cardiovascular toxicity. Low dose oestrogens in combination with antiandrogens or antithrombotic agents may be better tolerated treatments. The route of administration is a crucial factor in the genesis of cardiovascular toxicity and parenterally administered oestrogens may not entail the same risk. Further research in this area is warranted.
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PMID:Orchidectomy and oestrogen therapy revisited. 985 89

Castration or antiandrogen monotherapies remain options for prostate cancer treatment as only marginal benefits have been demonstrated with combined androgen blockade, although it may be that certain subgroups of patient may benefit. Of the nonsteroidal antiandrogens, bicalutamide 150 mg was as effective as castration in M0 patients with significant improvement in sexual interest and physical capacity, but the trial has yet to reach maturity. In M1 patients, bicalutamide 150 mg was not as effective as castration but this may be outweighed by symptomatic and quality of life benefits. Nilutamide is not recommended as monotherapy and there are little data on flutamide. The steroidal antiandrogen, cyproterone acetate, is as effective as oestrogen therapy and has a better side-effect profile, although cardiovascular and hepatic side effects are still of concern. Compared with flutamide, in a recently completed EORTC study, side effects such as gynaecomastia, diarrhoea, nausea, and liver function deterioration occurred less often, and thrombotic effects more often, in the cyproterone acetate group. No difference was seen in the preservation of sexual functioning. Quality of life issues are becoming increasingly important and thus antiandrogen monotherapy may become more widely used in the management of prostate cancer.
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PMID:Antiandrogens as monotherapy for prostate cancer. 985 90

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


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