![]() | Only 14 pages are availabe for public view |
Abstract In males, androgens are synthesized by the testes and by the adrenal gland. The testes are the major source of testosterone, while the androgens produced by the adrenal gland are hormone precursors that are enzymatically converted to testosterone and dihydrotestosterone in prostatic and peripheral tissues. Huggins and Hodges first established the role of androgen deprivation therapy (ADT) in prostate cancer in the early 1940s, resulting in the award of the 1966 Nobel Prize in Physiology or Medicine. They demonstrated that, in a patient with advanced PCa, surgical castration delayed tumour progression. Soon thereafter, it was learned that administration of estrogens, with central suppression of luteinizing hormone releasing hormone (LHRH) and peripheral production of testosterone, was an equally effective form of hormonal therapy. Early ADT indeed has a survival advantage over delayed ADT. Also early ADTallow PCa patients to avoid complications such as obstructive voiding symptoms, obstructive renal failure, and pain. The cost to the patient for the use of early therapy has been the well-established long-term side effects of ADT, including sexual dysfunction, cognitive changes, lethargy, bone demineralization, and metabolic syndrome. The disadvantages of ADThave led researchers to search for strategies to reduce negative treatment effects and to improve outcomes. Intermittent androgen suppression seems to be emerging as one such strategy. The first clinical report of the use of IAD was authored by Klotz et al. in 1986. They reported that withdrawal of diethylstilbestrol from patients with metastatic PCa after initial clinical response led to a reduction in the side effects Treatment was reinitiated after the patients became symptomatic again, and all patients experienced a rapid clinical response to treatment. Androgen deprivation achieved by luteinizing hormone-releasing hormone (LHRH) with or without an antiandrogen is expensive. Many patients are now being diagnosed with early or progressive disease on the basis of a rising PSA level alone, and hormonal therapy is being employed earlier in the course of disease. As a consequence, many patients are being treated with hormonal therapy at the asymptomatic stage and, by virtue of the natural history of the disease, survive for years after diagnosis. Hormone therapy given intermittently (with breaks) has proven to be as effective as hormone therapy given continuously in asymptomatic men with rising PSA levels after prostate cancer treatment, Hormone therapy also called androgen deprivation therapy is designed to block testosterone from stimulating the growth of hormonedependent types of prostate cancer. Because continuous androgen deprivation therapy produces side effects such as osteoporosis, hot flashes, and loss of libido, and because many prostate cancers eventually become resistant to hormonal therapy, researchers continue to explore alternatives. Intermittent hormone therapy is an alternative method of delivering treatment. With intermittent treatment, men receive hormonal therapy until they achieve a sufficient treatment response and then they take a break and have a period of no treatment. The cycle is repeated as needed. Intermittent hormone therapy may reduce side effects and delay hormone resistance. There isevidence that IAD is “non-inferior” to continuous androgen ablation in terms of time to progression and overall survival, and evidence is accumulating to suggest that IAD offers significant quality-of-life benefits, particularly with regard to sexual function during the offtreatment phase. IAD represents significant savings, in terms both of reduced medication needs and of reduced costs for managing the complications of prolonged CAS. |