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Principles of systemic treatment
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
None of the individual anti-androgen treatments offer complete blockade of both testicular and adrenal androgens. This may be achieved by combining a centrally acting gonadotrophin-releasing hormone agonist/antagonist, e.g. goserelin, with a peripherally acting drug such as cyproterone or bicalutamide, and this is known as ‘maximal androgen blockade – MAB’. This may be slightly more effective than single drug therapy in advanced disease, particularly in younger patients, but it is associated with more severe toxicity from androgen withdrawal, including lethargy, hot flushes, gynaecomastia and loss of sexual interest and function.
HORMONAL THERAPY OF CANCER
Published in James Bishop, Cancer Facts, 1999
Conflicting results have been obtained in studies comparing medical or surgical orchidectomy with an additional antiandrogen. This approach is known as maximum androgen blockade. A recent meta- analysis showed that if there was any benefit for the combined treatment, it was small.
Management of bone pain
Published in Nigel Sykes, Michael I Bennett, Chun-Su Yuan, Clinical Pain Management, 2008
Prostate cancer in virtually all cases is androgen-dependent at the time of presentation. Hormone therapy therefore aims to block androgen activity either pharmacologically using oral anti-androgens such as bicalutamide or flutamide, gonadotrophin-releasing hormone analogs such as goserelin or leuprolide, or surgical castration by orchidectomy. These individual methods of androgen ablation have been compared in multicenter randomized trials47, 48 [II] and no advantage for one against the other has emerged. Similarly, whilst there have been advocates for “maximal androgen blockade,” incorporating a central androgen blockade, such as goserelin, with peripheral androgen blockade using an oral anti-androgen drug metaanalysis49[II] suggests there is no significant advantage for maximal androgen blockade in patients with metastatic disease. Single agent anti-androgen therapy is therefore indicated with response rates of 80 to 90 percent for pain relief which may occur dramatically within 24 hours of starting treatment. The duration of response to androgen therapy is limited with an average duration of two to three years, during which time androgen-independent cells emerge; further short-lived responses may be obtained by switching to second-line hormone therapy or adding a second anti-androgen to achieve maximal androgen blockade. Chemotherapy using single agent taxotere has been shown to improve quality of life and extend survival by two months in this group of patients.50[II] It is in this group of “hormone-resistant” patients that wide field irradiation and systemic isotope therapy has been widely evaluated and has a major role.
Digital PET/CT with 18F-FACBC in early castration-resistant prostate cancer: our preliminary results
Published in Expert Review of Medical Devices, 2022
Luca Filippi, Oreste Bagni, Orazio Schillaci
Until 2018, standard treatment of nmCRPC mainly consisted of maximal androgen blockade through the addition of 1st generation anti-androgen (bicalutamide) plus androgen deprivation therapy (ADT). In recent years, nmCRPC therapeutic landscape has been thoroughly changed by the introduction of 2nd generation anti-androgens (i.e. apalutamide, darolutamide and enzalutamide) [3]. Phase 3 SPARTAN and PROSPER trials, in fact, demonstrated the efficacy of apalutamide and enzalutamide, respectively, to prevent the development of metastases in nmCRPC with a PSA doubling time (PSAdt) ≤10 months [4,5]. More recently, the clinical trial ARAMIS supported the introduction of another 2nd generation anti-androgen (i.e. darolutamide) for the clinical management of nmCRPC [6].
Ionizing Radiation Combined with PARP1 Inhibitor Reduces Radioresistance in Prostate Cancer with RB1/TP53 Loss
Published in Cancer Investigation, 2021
Yao Fan, Hui Fan, Zhen Quan, XiaoHou Wu
Prostate cancer (PC) is the most frequently diagnosed cancer among men in Western countries (1). Although second-generation antiandrogens have been designed to achieve maximal androgen blockade, treatment of patients with castration-resistant prostate cancer (CRPC) presents new challenges for long-term disease control (2). Radiotherapy has long been a therapeutic option for patients with advanced prostate cancer, especially when combined with androgen deprivation therapy (ADT) (3). However, prostate cancer in a large number of patients develops resistance against radiotherapy. Moreover, the increasing dose of IR along with this radio-resistance could also cause severe damage to normal tissues and subsequently increase the risk of occurrence of second cancer (4,5). Therefore, the unraveling of molecular mechanisms underlying radiation resistance could improve radiosensitivity and reduce the adverse effects of treatment.
Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study
Published in Acta Oncologica, 2019
Frederik Birkebæk Thomsen, Cecilia Bosco, Hans Garmo, Jan Adolfsson, Niklas Hammar, Pär Stattin, Mieke Van Hemelrijck
The current EAU-ESTRO-SIOG guidelines do not recommend AA with bicalutamide 150 mg/daily as standard of care for men with high-risk PCa with no distant metastasis [1]. This recommendation is based on a Cochrane review, which concluded that AA in men with advanced PCa is less effective than castration in terms of overall survival [17]. However, this review included studies with different types of AA and different dosages. Furthermore, in the subgroup analysis of men with advanced, non-metastatic PCa treated with bicalutamide 150 mg/daily, overall survival was similar to castration, in line with two randomised controlled trials (RCTs) [18,19]. These two RCTs specifically compared the clinical effectiveness as well as adverse events of bicalutamide 150 mg/daily versus GnRH agonists or maximal androgen blockade (GnRH agonist combined with continuous AA). Although the statistical requirement for non-inferiority was not met, survival was similar between the group of men treated GnRH agonists and those treated with bicalutamide 150 mg/daily. Based on these trials, the European Medicines Agency subsequently approved this AA for use in men with advanced, non-metastatic PCa [20].