Hormonal therapy, although effective as single therapy, may also be combined with other therapies and as an alternative to observation. The prostate is a hormone-responsive organ, which is the basis for this prostate cancer therapy. The hormonal therapy either reduces the serum androgens (testosterone and dihydrotestosterone) or blocks the actions of these hormones. The expected effect is an apoptotic regression of the tumour as a consequence of the antagonistic effect on the androgen receptor. These systemic hormonal treatment approaches cause a broad range of side-effects that limit the quality of life.
Nevertheless, in early prostate cancer there has been an enhanced prescription of oral antiandrogens during the last 5–10 years. This prescription trend is expected to continue as a consequence of the increased use of plasma PSA as a screening tool that will lead to more patients diagnosed with early prostate cancer.
Although androgen deprivation as a treatment for patients with prostate cancer has been an important cornerstone during more than five decades its optimal clinical use remains controversial. The widespread use of PSA assay in plasma samples has lead to earlier diagnosis and earlier detection of recurrent disease. Accordingly, there are a growing number of patients with an early and localised prostate cancer, which means that the extensive systemic side-effects of androgen deprivation and quality of life have become even more important to consider.
The most commonly used oral antiandrogen therapy today is bicalutamide (Casodex®) from AstraZeneca and flutamide (Eulexin®, Schering-Plough, Eulecin®, Flutacan®, Flutamid®). The side-effect spectrum of bicalutamide and flutamide, although bicalutamide showing less severe and less numerous side-effects, includes diarrhoea, breast enlargement, nausea, impotence, reduced or loss of libido, abdominal pain, flatulence, tiredness, asthenia, osteoporosis, sweating, hot flushes, weight gain and liver toxicity, and consequently a decreased quality of life. These side-effects following oral antiandrogen therapy are to a major extent dose and plasma concentration related, and thus dependent on high levels of the active drug in the systemic circulation and other tissues than the prostate tissue.
Importantly, none of these unacceptable side-effects are mediated by a local treatment in the prostate tissue as the systemic drug concentration will be significantly reduced. Hence, it is an attractive approach to focus on a novel therapeutic implant drug delivery system that aims to optimize the local prostatic concentration/amount versus time profile of the active drug, thereby increasing the anticancer action in the target tissue, and at the same time reduce the systemic drug concentrations and the consequential, unacceptable side-effects.