Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer
Status:
Completed
Trial end date:
2014-01-01
Target enrollment:
Participant gender:
Summary
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.