Prospective study relating genotype profiles with race performance in racing pigeons.

This is a prospective study to investigate the impact of genotype profiles on race performance in racing pigeons. Genotypes studied included lactate dehydrogenase A (LDHA), dopamine receptor (DRD), myostatin (MSTN), and feather keratin (F-KER), as well as demographic factors such as gender, color, and the mtDNA. This study shows differences within genotypes DRD456 (P = 0.

The myth of mitochondrial DNA and race performance in racing pigeons.

This is the first prospective study to investigate the impact of mitochondrial DNA (mtDNA) on race performance in a closely bred family of racing pigeons in one breeding loft where there is a high percentage of male and female birds related to one foundation hen, Queen L by Jelle Roziers. This study shows that in this family of birds, which are all related to Queen L, there is no advantage of having mtDNA with regard to race performance on the longer distances. The results of this study reject the hypothesis that mtDNA genes are related to long-distance performance.

Will the experience with tamoxifen in breast cancer help define the role of antiandrogens in prostate cancer?

Breast and prostate cancers are the two predominant hormone-responsive tumours. The use of the antioestrogen tamoxifen in the treatment of breast cancer has evolved over the past 30 y from treatment for advanced breast cancer to prevention. Tamoxifen is currently the endocrine treatment of choice for advanced breast cancer and for adjuvant therapy in a broad spectrum of women whose primary tumours have functional oestrogen receptors.

Receptor affinity and potency of non-steroidal antiandrogens: translation of preclinical findings into clinical activity.

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.

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program.

Purpose: We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.

Materials And Methods: This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg.

Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer.

Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quality-of-life benefits over conventional treatment modalities. Of available antiandrogens, monotherapy with bicalutamide has been most extensively evaluated.

Androgen antagonists: Potential role in prostate cancer prevention.

This article summarizes discussions of the importance of androgens and androgen antagonists in the genesis of prostate cancer. These discussions occurred at a recent symposium on prostate cancer chemoprevention sponsored by the National Cancer Institute. Considerable information exists indicating the importance of androgens in the development of prostate cancer.

Does prolonged combined androgen blockade have survival benefits over short-term combined androgen blockade therapy?

Objectives: To explore whether less than 120 days of an antiandrogen plus a luteinizing hormone-releasing hormone agonist resulted in a different survival outcome than 120 days or more of combined treatment in patients with Stage D2 prostate cancer.

Methods: Survival data were available from a previously published controlled trial that had evaluated the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with a monthly depot preparation of leuprolide or goserelin, in 813 patients with Stage D2 prostate cancer. Cox's proportional hazards regression model assessed the relative effects of the length of combined androgen blockade (CAB) therapy on survival.

Exploratory analysis on the effect of race on clinical outcome in patients with advanced prostate cancer receiving bicalutamide or flutamide, each in combination with LHRH analogues. The Casodex Combination Study Group.

Background: Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB).

Methods: Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.

Bicalutamide dosages used in the treatment of prostate cancer.

Background: Androgen deprivation is often used for the treatment of patients with prostate cancer. Androgen deprivation can be achieved by surgical castration or medical castration, with or without using an antiandrogen. Each of these treatments may be used alone, or an antiandrogen may be used alongside castration to produce combined androgen blockade therapy.

Comparison of goserelin and leuprolide in combined androgen blockade therapy.

Objectives: To perform exploratory analyses of data from a controlled trial that assessed the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with monthly depot preparations of leuprolide or goserelin, in patients with Stage D2 prostate cancer. One analysis compared goserelin plus antiandrogen therapy with leuprolide plus antiandrogen therapy; a second analysis compared the four combined androgen blockade (CAB) regimens.

Methods: This was a randomized, multicenter trial, open-label for luteinizing hormone releasing hormone analogue (LHRH-A) therapy, double-blind for antiandrogen therapy, with a two-by-two factorial design.

Bicalutamide (Casodex) in the treatment of prostate cancer: history of clinical development.

Background: Bicalutamide (Casodex) is a new nonsteroidal antiandrogen developed for use in patients with prostate cancer. The efficacy and tolerability of bicalutamide as monotherapy and as combination therapy for patients with advanced prostate cancer have been evaluated in randomized clinical trials. Clinical trials are currently in progress to further evaluate bicalutamide as monotherapy in patients with advanced stages of disease and as adjuvant or first-line therapy in patients with early-stage disease.

High dose bicalutamide for androgen independent prostate cancer: effect of prior hormonal therapy.

Purpose: A pilot study of the antiandrogen bicalutamide at 150 mg. a day for androgen independent prostate cancer was performed. This study was based on the possibility that androgen independent cases might display responses to additional hormonal agents.

Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group.

Objectives: To compare the efficacy and tolerability of bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with metastatic (Stage D2) prostate cancer.

Methods: This was a randomized, double-blind (for antiandrogen therapy), multicenter study with a two-by-two factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.

Functional characterization of mutant androgen receptors from androgen-independent prostate cancer.

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.

Bicalutamide for advanced prostate cancer: the natural versus treated history of disease.

Purpose: To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities.

Methods: Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups.

Prostate specific antigen decreases after withdrawal of antiandrogen therapy with bicalutamide or flutamide in patients receiving combined androgen blockade.

Purpose: We determined whether decreases in prostate specific antigen (PSA) would occur after withdrawal of double-blinded antiandrogen therapy with flutamide or bicalutamide for clinical progression or increasing PSA concentration in patients receiving combined androgen blockade for advanced prostate cancer.

Materials And Methods: PSA concentrations were determined weekly for at least 6 weeks and then every other week for 6 weeks in 22 patients with stage D2 prostate cancer. All patients were withdrawn from antiandrogen therapy (8 flutamide and 14 bicalutamide) due to progression or an increasing PSA concentration.

The antiandrogen withdrawal syndrome in relapsed prostate cancer.

Evolving data suggest that palliation of relapsed prostate cancer can be achieved by the selective discontinuation of agents that act via steroid hormone receptors. Clinical benefit has been observed following the withdrawal of flutamide (Eulexin, Schering-Plough International), bicalutamide (Casodex, Zeneca Ltd), oestrogens, progestational agents and retinoids. For patients with progression of disease while receiving these drugs, a period of observation after withdrawal should be considered before further therapy is initiated.

Three-month depot of goserelin acetate: clinical efficacy and endocrine profile. Dutch South East Cooperative Urological Group.

Objectives: To compare the pharmacodynamics and tolerability of the new goserelin acetate 10.8-mg depot with the 3.6-mg depot in patients with advanced prostate cancer during the first 3 months of therapy.

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group.

Background: A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death.

Methods: Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.

Bicalutamide: a new antiandrogen for use in combination with castration for patients with advanced prostate cancer.

Maximum androgen blockade, a relatively recent development in the treatment of prostate cancer, combines medical or surgical castration with antiandrogen therapy. A large randomized study comparing the non-steroidal antiandrogen, bicalutamide, with flutamide, each in combination with luteinizing hormone-releasing hormone (LHRH) analogs, showed that after a median follow-up of 49 weeks, the time to treatment failure was significantly longer for the bicalutamide patients compared with the flutamide patients (p = 0.005).

A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group.

Between January 1992 and September 1993, 813 patients with stage D2 prostate cancer were enrolled in a multicentre, double-blind (for antiandrogen therapy) trial and randomised to antiandrogen therapy with Casodex (bicalutamide, 50 mg once daily) or flutamide (250 mg three times daily) and to luteinising hormone-releasing hormone (LHRH) analogue therapy with Zoladex (goserelin, 3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days).

Defining the role of antiandrogens in the treatment of prostate cancer.

Objectives: Although antiandrogens have been used as monotherapy and in combination with other treatment modalities for management of metastatic prostate cancer, their major role to date has been one in which they are used in conjunction with surgical or medical castration for treatment of Stage D (T4/Nx/M1) carcinoma of the prostate. The widespread use of prostate-specific antigen (PSA) is increasing the number of men who are diagnosed with earlier stages of this disease, thus resulting in a greater number of definitive therapeutic procedures. Also, PSA has become the primary modality for following these patients after definitive treatment.