Track topics on Twitter Track topics that are important to you
Prostate cancer (CaP) is the most commonly diagnosed cancer among males in the U.S. and the second leading cause of cancer-related mortality. More than 230,000 men will be diagnosed with prostate cancer in the USA this year and more than 30,000 will die of this disease.
Androgen deprivation, the elimination of testosterone and its active metabolites, remains the single most effective intervention available for the treatment of advanced prostate carcinoma. This is usually achieved by surgical removal of the testes (orchiectomy), by suppressing production of testosterone (LHRH agonists) and/or by blocking the androgens at receptor sites (antiandrogens). Unfortunately, androgen suppression does not cure the disease. Most patients progress within 0-5 years, and all patients ultimately progress if the cancer is not eliminated during initial therapy (usually prostatectomy or radiation).
Hormone suppression treatment eliminates the detectable levels of testosterone in the blood. However, the testosterone levels in tissue remain high enough to stimulate androgen receptors. Overexpression of androgen receptors is present in all cell lines which demonstrate "androgen independence," i.e., are resistant to androgen-suppressive therapy.
Approximately 95% of testosterone is supplied by the testes, with the remaining 5% supplied by the adrenal glands. The presumption that standard androgen deprivation achieves the optimal level of androgen suppression for patients is based on the levels of androgen which result from orchiectomy. However, because adrenal androgen levels are unaffected by standard modes of androgen deprivation, 5% of the body's testosterone remains despite hormone therapy.
The hypothesis of this study is that more effective suppression of the androgen axis through elimination of adrenal androgens and more effective suppression of testosterone metabolites will lower intraprostatic androgen levels, minimizing activation of the androgen receptor and augmenting natural cell death (apoptosis). The investigators propose to test this hypothesis by administering neoadjuvant (pre-surgery) androgen deprivation therapy of different types before prostatectomy for patients with clinically localized prostate cancer. The investigators will assay serum and intraprostatic androgen levels, while assessing relative levels of apoptosis of normal and malignant tissue.
Androgen deprivation has been the principal means of controlling advanced prostate cancer, but does not cure the disease and all patients ultimately progress if the tumor is not eliminated with definitive local therapy. It has been demonstrated that despite androgen deprivation with LHRH agonists or orchiectomy, prostate tissue and prostate cancer maintain levels of androgens which are more than adequate to stimulate the androgen receptor. These levels of androgen may continue to stimulate the receptor and allow both survival of tumor cells and induction of resistance by overexpression of the receptor. The presumption that standard androgen deprivation achieves the optimal level of androgen suppression for patients is based on the levels of androgen achieved with castration, which achieves relatively short term control of cancer in the majority of patients. The hypothesis of this study is that more effective suppression of the androgen axis through elimination of adrenal androgens and more effective suppression of conversion to dihydrotestosterone will lower intraprostatic androgen levels, minimizing activation of the androgen receptor and augmenting apoptosis. We propose to test this hypothesis in a prospective, randomized trial, administering neoadjuvant androgen deprivation therapy of different types prior to radical prostatectomy for patients with clinically localized prostate cancer for 3 months.
Plan of therapy
Patients with clinically localized (cT1-T2) prostate cancer, at intermediate-high risk for relapse who are candidates for radical prostatectomy will be treated with one of three regimens:
- Goserelin with dutasteride
- Goserelin with bicalutamide and dutasteride
- Goserelin with bicalutamide and dutasteride and ketoconazole
Patients will undergo radical prostatectomy 3 months after initiation of treatment.
Preoperative and intraoperative biopsies of the prostate gland will be utilized for analysis of prostatic hormones, gene expression and apoptosis.
Allocation: Randomized, Control: Active Control, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
goserelin with dutasteride, goserelin with bicalutamide and dutasteride, goserelin with bicalutamide and dutasteride and ketoconazole
University of Washington
Active, not recruiting
University of Washington
Published on BioPortfolio: 2014-08-27T03:45:51-0400
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Bicalutamide and goserelin may fight prostate cancer by reducing the production of testosterone. It is not yet k...
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways may cause less damage to normal tissue and may improve quality of lif...
This is a therapeutic trial study to demonstrate whether Goserelin, a LHRH agonist has benefit in SBMA Objective: 1. To study effects of Goserelin to clinical course of patients ...
This randomized phase II trial is studying bicalutamide, goserelin, or leuprolide acetate to see how well they work when given with or without cixutumumab in treating patients with newly d...
Avodart (dutasteride) reduces the male hormone (DHT) that leads to prostate growth and stimulates cancerous growth. Avodart is currently approved by the FDA to treat men with symptoms of a...
Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III...
The 5-α-reductase inhibitors finasteride and dutasteride are frequently used in the treatment of androgenetic alopecia and benign prostatichyperplasia. These drugs are effective at reducing levels of...
To investigate whether use of dutasteride, a 5-alpha reductase inhibitor, for at least four weeks preoperatively affected the blood loss during open prostatectomy (OP).
The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined.
A synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE. Goserelin is used in treatments of malignant NEOPLASMS of the prostate, uterine fibromas, and metastatic breast cancer.
A 5-ALPHA-REDUCTASE INHIBITOR that is reported to inhibit both type-1 and type2 isoforms of the enzyme and is used to treat BENIGN PROSTATIC HYPERPLASIA.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Prostate cancer (cancer de prostata) Prostate cancer (cancer de prostata) is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostat...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...