An update on bicalutamide in the treatment of prostate cancer

Abstract

In this update, bicalutamide (Casodex, Zeneca Pharmaceuticals) has been confirmed as an effective, well-tolerated and convenient non-steroidal anti-androgen for advanced prostate cancer. Preclinical and clinical studies have indicated its potential as monotherapy, with quality of life advantages compared with castration. A head-to-head comparison with flutamide, where both anti-androgens were used as part of combined androgen blockade, has suggested that the choice of components in this regimen can influence outcome, and has demonstrated that bicalutamide is better tolerated than flutamide. There is also preliminary evidence to support the potential use of bicalutamide in treatment of early-stage disease and tumours that are refractory to other non-steroidal anti-androgens.

Development of Androgen-Antagonistic Coumarinamides with a Unique Aromatic Folded Pharmacophore

“…However, AR antagonists bearing a steroid core structure have undesirable side effects due to their cross-activity with other steroid hormone receptors. Consequently, nonsteroidal AR antagonists have been developed, and some of them, such as flutamide (2a) [8] and bicalutamide (BIC, 3, Figure 1) [9,10], are in clinical use to treat prostate cancer. These first-generation nonsteroidal AR antagonists are effective for most prostate cancer patients, but castration-resistant prostate cancer (CRPC) often develops after a few years, due to the mutation of AR [11][12][13].…”

Design and synthesis of 4-benzyl-1-(2H)-phthalazinone derivatives as novel androgen receptor antagonists

“…For example, we have reported two AR antagonists without the anilide-type pharmacophore, i.e., (Z)-4-(4-diethylaminophenylmethylene)-3-phenyl-5(4H)-isoxazolone (5, Figure 2) 17 and 4-(N-benzyl-N-nitrophenyl)aminopyrrole-2-carboxamide (6). 18 These compounds showed high binding affinity for wild-type (wt) AR, and were effective in LNCaP cells bearing T877A-mutated AR.…”

“…1,2 AR modulates multiple physiological phenomena, including differentiation, growth, and maintenance of male reproductive organs, and also has effects on hair and skin (androgenic effects). 3,4 Since androgen plays an important role in progression of prostate cancer, 5 various AR antagonists have been investigated for treatment of prostate cancer, and some of them have been brought into clinical use, including bicalutamide (1, Figure 1) 6 and flutamide (2). 7 Although hormone therapy using AR antagonist or combined androgen blockade therapy is effective for most prostate cancer patients, its efficacy decreases after a few years of treatment, with the development of so-called castration-resistant prostate cancer (CRPC).…”

Novel Flufenamic Acid Analogues as Inhibitors of Androgen Receptor Mediated Transcription

“…Additionally, tumors treated with anti-androgens become resistant to that therapy within several years of treatment ( 16–18 ) . For these reasons current pharmacological strategies targeting AR are focused on the development of SARMs (selective Androgen Receptor Modulators) that interact with the ligand binding pocket of AR and regulate AR mediated gene transcription in a tissue selective manner ( 19–20 ) .…”