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)

The utility of monotherapy with antiandrogens in prostate cancer is under investigation. Flutamide (Eulexin, Schering-Plough International) appears equally effective to castration in prolonging progression-free survival. Nilutamide (Anandron, Roussel) has been studied less widely, but may represent a valid treatment option in advanced prostate cancer. Preliminary results suggest that bicalutamide (Casodex, Zeneca Ltd) is as effective as castration in non-metastatic disease. Monotherapy with non-steroidal antiandrogens may offer successful palliative management of advanced prostate cancer with significant value in enhancing certain aspects of quality of life.
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PMID:Antiandrogen monotherapy in the management of advanced prostate cancer. 907 6

Prostate cancer, acne, seborrhea, hirsutism, and androgenic alopecia are well recognized to depend upon an excess or increased sensitivity to androgens or to be at least sensitive to androgens. It thus seems logical to use antiandrogens as therapeutic agents to prevent androgens from binding to the androgen receptor. The two predominant naturally occurring androgens are testosterone (T) and dihydrotestosterone (DHT). DHT is the more potent androgen in vivo and in vitro. All androgen-responsive genes are activated by androgen receptor (AR) bound to either T or DHT and it is believed that AR is more transcriptionally active when bound to DHT than T. The two classes of antiandrogens, presently available, are the steroidal derivatives, all of which possess mixed agonistic and antagonistic activities, and the pure non-steroidal antiandrogens of the class of flutamide and its derivatives. The intrinsic androgenic, estrogenic and glucocorticoid activities of steroidal derivatives have limited their use in the treatment of prostate cancer. The non-steroidal flutamide and its derivatives display pure antiandrogenic activity, without exerting agonistic or any other hormonal activity. Flutamide (89) and its derivatives, Casodex (108) and Anandron (114), are highly effective in the treatment of prostate cancer. The combination of flutamide and Anandron with castration has shown prolongation of life in prostate cancer. Furthermore, combined androgen blockade in association with radical prostatectomy or radiotherapy are very effective in the treatment of localized prostate cancer. Such an approach certainly raises the hope of a further improvement in prostate cancer therapy. However, all antiandrogens, developed so-far display moderate affinity for the androgen receptor, and thus moderate efficacy in vitro and in vivo. There is thus a need for next-generation antiandrogens, which could display an equal or even higher affinity for AR compared to the natural androgens, and at the same time maintain its pure antiandrogenic activity, and thus providing improved androgen blockade using possibly antiandrogens alone.
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PMID:Androgen receptor antagonists (antiandrogens): structure-activity relationships. 1063 63

The non-steroidal antiandrogens flutamide (Eulexin((R))), nilutamide (Anandron((R))) and bicalutamide (Casodex((R))) are widely used in the treatment of advanced prostate cancer, particularly in combination with castration. The naturally occurring ligand 5alpha-DHT has higher binding affinity at the androgen receptor than the non-steroidal antiandrogens. Bicalutamide has an affinity two to four times higher than 2-hydroxyflutamide, the active metabolite of flutamide, and around two times higher than nilutamide for wild-type rat and human prostate androgen receptors. Animal studies have indicated that bicalutamide also exhibits greater potency in reducing seminal vesicle and ventral prostate weights and inhibiting prostate tumour growth than flutamide. Although preclinical data can give an indication of the likely clinical activity, clinical studies are required to determine effective, well-tolerated dosing regimens. As components of combined androgen blockade (CAB), controlled studies have shown survival benefits of flutamide plus a luteinising hormone-releasing hormone analogue (LHRH-A) over LHRH-A alone, and for nilutamide plus orchiectomy over orchiectomy alone. Other studies have failed to show such survival benefits, including those comparing flutamide plus orchiectomy with orchiectomy alone, and nilutamide plus LHRH-A with LHRH-A alone. In a direct comparative study, bicalutamide (50 mg, once daily) was compared with flutamide (250 mg, three times daily), each in combination with an LHRH-A. Both therapies were well tolerated, although more patients could not tolerate flutamide therapy: 25 flutamide plus LHRH-A and 2 bicalutamide plus LHRH-A patients withdrew from therapy due to diarrhoea. There were no statistically significant differences for time to progression or survival between the two antiandrogens. This clinical trial of bicalutamide confirms the prediction from preclinical studies that a 50 mg dose of bicalutamide would be appropriate for use in patients with advanced prostate cancer, and demonstrates that this bicalutamide dose is clinically effective when administered as part of CAB.
Prostate Cancer Prostatic Dis 1998 Dec
PMID:Receptor affinity and potency of non-steroidal antiandrogens: translation of preclinical findings into clinical activity. 1249 72

The use, tolerability and efficacy of the non-steroidal anti-androgen nilutamide (Anandron(R)) in daily clinical practice was investigated in this 5-y project. In total 725 patients were recruited from 27 Dutch centres. The investigated population was very heterogeneous and different therapeutic options were reported. We may conclude that in general good results have been obtained, especially in first line combination therapy combined with luteinising hormone releasing hormone (LHRH) agonists. Patients with a good performance status at inclusion seem to benefit more from nilutamide combination therapy.Prostate Cancer and Prostatic Diseases (2001) 4, 112-117
Prostate Cancer Prostatic Dis 2001
PMID:Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide. 1249 48

The use of maximum androgen blockade (MAB) in advanced prostate cancer remains controversial due to conflicting data from clinical trials. Some of the trials that report no advantage of MAB over monotherapy have been criticized on a number of points, including a lack of statistical power and too short a follow-up period. Three randomized trials, SWOG-INT 0036, EORTC-30853 and the Anandron Study Group Trial, report a survival advantage and a longer time to disease progression with MAB, although only one reaches statistical significance. The widespread use of MAB is controversial on the basis of the available clinical data. It has been suggested that three clinical situations exist for its use in advanced cancer: in symptomatic disease; as neoadjuvant therapy prior to radiotherapy; and for the prevention of flare following the use of luteinizing-hormone-releasing hormone analogues as monotherapy. Case studies are presented in this article involving the use of MAB in these circumstances, as well as its use under other conditions. MAB fits into an algorithm of progressive step-up therapy and by tailoring hormonal therapy to individual patients and their tumours we may improve survival and define further the future role of MAB. Prostate Cancer and Prostatic Diseases (2000) 3, 203-212
Prostate Cancer Prostatic Dis 2000 Nov
PMID:Maximum androgen blockade: a case study report. 1249 99


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