Primary Androgen Deprivation Research Articles

Secondary hormonal manipulation of prostate cancer.

Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases develop disease progression. Patients with hormone-resistant prostate cancer (HRPC) have a median survival of approximately 18 months, and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease, and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone.

Treatment options in hormone-refractory prostate cancer: current and future approaches.

Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases will develop disease progression. Patients with hormone refractory prostate cancer (HRPC) have a median survival of approximately 18 months and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone. Until recently, cytotoxic chemotherapy was felt to be relatively ineffective in the treatment of HRPC. Combination regimens incorporating new active agents have demonstrated significant activity in this setting, renewing interest in the use of chemotherapy to treat HRPC. Recent advances in the understanding of prostate cancer biology have led to the development of drugs directed against precise molecular alterations in the prostate tumour cell. Biologic agents now in development include those capable of altering signal transduction, blocking angiogenesis, inhibiting cell cycle progression, and stimulating apoptosis. In addition, many types of immune therapies are showing promise. Evaluating these agents, and incorporating them into existing regimens, are major goals of ongoing clinical research in advanced prostate cancer.

Maximale Androgenblockade

According to the representative data of the Tumor Registry Munich, 38.1 % of prostate cancer patients received a primary androgen deprivation, whereas 20.5 % had an adjuvant hormonal treatment. Following surgical castration being the most common form of androgen deprivation, 5 alpha-dihydrotestosterone is still present in prostate cancer tissue. Therefore, a maximal androgen blockade (MAB) consisting of a chemical or surgical castration plus a pure or antigonadotropic antiandrogen, has been proposed. Indeed, MAB lowers the dihydrotestosterone-androgen-receptor complex and suppresses the growth-factor dominated signal transduction. This leads to a measurable increase of apoptosis. New is the finding that LHRH as well as LH (for example following surgical castration) are bound by receptors located at the prostate cancer cell. In 30 phase-III trials, MAB has been tested against monotherapy and a cancer-specific survival advantage of 3 to 6 months and a approximately 6-month delay of progression was demonstrated. The most effective form of MAB is the combination of a LHRH agonist - in contrast to surgical castration - with a well-tolerated pure antiandrogen. The quality of life during MAB is low, if a pure antiandrogen such as flutamide is used which leads to rather serious side-effects. At the present time, special indications for MAB are patients with minimal metastases, bone pain at the time of diagnosis, a neoadjuvant or adjuvant application in combination with a radical prostatectomy or radiotherapy and particularly intermittent androgen deprivation which is tested at the present time in at least 5 international studies. An endocrine withdrawal syndrome is observed in approximately 30 % of patients, if, following a PSA-relapse, the antiandrogen is discontinued. Little notice has been given to the use of prognosticators for the decision, whether a MAB is useful or not. Patients with good prognostic factors as defined by Sylvester have a clear advantage, if MAB is compared to monotherapy, whereas patients with a pure prognosis did not benefit. In addition to these prognostic factors up-front, the PSA dynamics under an initial MAB may be employed for the decision, if this form of androgen deprivation is to be continued or not. In essence, in contrast to a general use of MAB a more differential application based on quality-of-life issues and prognosis should be preferred.

Therapy of hormonerefractory cancer of the prostate

In patients with hormone-resistant prostate cancer primary androgen deprivation eventually fails. The begin of secondary treatment is depending on clinical symptoms; since survival cannot be prolonged in progressive disease improvement of quality of life is of paramount importance. Altering of endocrine treatment and antiandrogen withdrawal can cause a transient improvement of the sense of well being. Single agent chemotherapy with little side effects should be preferred as compared with polychemotherapy since response rates do not exceed 30%. Although 2/3 of the patients benefit from chemotherapy there is however no proof that it is superior to symptom-related pain relief. The indication for surgical management such as TURP and spinal cord decompression is depending on clinical symptoms from local progression and systemic disease.

Future directions in prostate cancer treatment: An oncologist's perspective

Prostate cancer has become one of the most important national health problems, as its incidence increases yearly. Conventionally, single-modality local therapy has been the standard of care for clinically localized stage disease and systemic therapy, in the form of primary or combined androgen deprivation, is reserved for advanced, usually metastatic, prostate cancer. Despite improvements in local therapy, a significant number of patients with clinically localized prostate cancer will suffer a systemic relapse after potentially curative local therapy and, despite 50 years of experience in hormone therapy, significant survival prolongation for patients with metastatic prostate cancer remains a challenge. This paper explores potential future systemic therapy strategies in the treatment of prostate cancer. Specifically, the role of adjuvant systemic therapy as part of a multimodality treatment approach for localized prostate cancer and alternative applications of hormone and chemohormone therapies for patients with metastatic disease are discussed.