The Development of Casodex™
(Bicalutamide):
Preclinical Studies

Furr, B. J. A.

doi:10.1159/000473846

Cited by 68 publications

(56 citation statements)

References 34 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparative studies with the nonsteroidal anti-androgen bicalutamide, a "pure" anti-androgen that inhibits androgen-induced gene expression and cell growth, 44 revealed that the AR antisense ODN as750/15 is more effective in tumor cell growth inhibition than this commonly used nonsteroidal anti-androgen. These findings further demonstrate that down-regulation of AR expression by AR antisense ODNs might be more effective in tumor growth inhibition than AR inactivation by antiandrogen treatment.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides

et al. 2000

View full text Add to dashboard Cite

Currently available methods for treatment of human prostatic carcinoma aim to inactivate the androgen receptor (AR) by androgen deprivation or blockade with anti-androgens. Failure of endocrine therapy and tumor progression is characterized by androgenindependent growth despite high levels of AR expression in metastatic disease. We inhibited AR expression in LNCaP prostate tumor cells by using antisense AR oligodeoxynucleotides (ODNs) and explored whether antisense AR treatment would be conceivable as a therapy for advanced prostate cancer. Among the various AR antisense ODNs tested, a 15-base ODN targeting the CAG repeats encoding the poly-glutamine region of the AR (as750/15) was found to be most effective. Treatment of LNCaP cells with as750/15 reduced AR expression to ϳ2% within 24 hours compared with mock-treated controls. AR down-regulation resulted in significant cell growth inhibition, strongly reduced secretion of the androgen-regulated prostate-specific antigen, reduction of epidermal growth factor receptor expression, and an increase in apoptotic cells. Mis-sense and mismatched control ODNs had no or only slight effects. Antisense inhibition was also very efficient in LNCaP-abl cells, a subline established after long-term androgen ablation of LNCaP cells, resulting in inhibition of AR expression and cell proliferation that was similar to that seen for parental LNCaP cells. This study shows that inhibition of AR expression by antisense AR ODNs may be a promising new approach for treatment of advanced human prostate cancer. Cancer Gene Therapy (2000) 7, 997-1007

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides

et al. 2000

View full text Add to dashboard Cite

show abstract

“…No beneficial effects were observed for nil over flut and nil has the least favorable safety profile (Sarosdy 1999). While peripheral selectivity was observed in intact rats due to a low passage across the blood-brain barrier (Furr 1996), this was not the case in men with advanced PCa. Their serum LH and serum T levels were significantly increased due to bic therapy (Mahler & Denis 1990).…”

Section: Antiandrogensmentioning

confidence: 94%

Androgen receptor antagonists for prostate cancer therapy

Helsen¹,

Broeck²,

Voet³

et al. 2014

Endocrine-Related Cancer

123

View full text Add to dashboard Cite

Androgen deprivation is the mainstay therapy for metastatic prostate cancer (PCa). Another way of suppressing androgen receptor (AR) signaling is via AR antagonists or antiandrogens. Despite being frequently prescribed in clinical practice, there is conflicting evidence concerning the role of AR antagonists in the management of PCa. In the castration-resistant settings of PCa, docetaxel has been the only treatment option for decades. With recent evidence that castration-resistant PCa is far from AR-independent, there has been an increasing interest in developing new AR antagonists. This review gives a concise overview of the clinically available antiandrogens and the experimental AR antagonists that tackle androgen action with a different approach.

show abstract

“…Therefore, to standardize the collection of our baseline data and to spare the participants extra travel and effort, the first test session was scheduled to occur immediately prior to their appointments for the administration of their initial dose of GNRH-a. Given that bicalutimide has been shown to bind selectively to human prostate androgen receptors without stimulating the HPA axis (Furr, 1996), it is unlikely that bicalutimide affected cognitive functioning.…”

Section: Discussionmentioning

confidence: 99%

“…Bicalutimide is a nonsteroidal antiandrogen, devoid of other endocrine activity, that competitively inhibits the action of androgens by binding to cytosol androgen receptors in target tissue (Canadian Pharmacists Association, 2007). However, it has been established that bicalutamide is peripherally selective and has little effect on serum LH and T due to poor penetration across the blood-brain barrier (Furr, 1996). Estradiol-17β micronized E 2 1 mg/day (Estrace, Roberts Pharmaceutical Corporation, NJ).…”

Section: Drugsmentioning

confidence: 99%

A randomized controlled trial of add-back estrogen or placebo on cognition in men with prostate cancer receiving an antiandrogen and a gonadotropin-releasing hormone analog

Matousek

Sherwin

2010

Psychoneuroendocrinology

View full text Add to dashboard Cite

SummaryThe effects of testosterone (T) and estradiol (E 2 ) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E 2 on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0 ± 8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E 2 were suppressed. In the second phase of the study, either micronized E 2 1 mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E 2 would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E 2 -treated men, exhibited a trend towards improvement in their scores on both the immediate (p = . 075) and delayed recall (p = .095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E 2 -treated men on both the immediate (p = .020) and delayed recall (p = .016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E 2 failed to improve short-or long-term verbal memory performance in this sample of older men being treated for prostate cancer. KeywordsGonadotropin-releasing hormone analog; Estrogen; Cognition; Prostate cancer; Randomized controlled trial; Combined androgen blockade In healthy males, decreases in total, free, and bioavailable testosterone levels occur with advancing age (Nankin and Calkins, 1986;Gray et al., 1991;Morley et al., 1997;Morley, 2000;Harman et al., 2001;Snyder, 2001;Vermeulen, 2001 CIHR Author Manuscript CIHR Author ManuscriptCIHR Author Manuscript studies of changing hormone levels in elderly men have consistently found a 1-2% annual decline in free or bioavailable testosterone (Morley et al., 1997;Harman et al., 2001;Snyder, 2001;Vermeulen, 2001;Feldman et al., 2002), with the incidence of hypogonadism rising from 20% in 60-69-year-old men to 50% in those over 80 years of age (Harman et al., 2001). Moreover, since approximately 80% of circulating estradiol (E 2 ), the most potent estrogen, is aromatized from testosterone (T) in men (Kaufman and Vermeulen, 2005), there is a corresponding decline in total and bioavailable E 2 with increasing age (Ferrini and Barrett-Connor, 1998;Khosla et al., 1998;Van den Beld et al., 2000;Vermeulen et al., 2003).Estrogen (E) and T mediate aspects of learning and memory in rodents (Bimonte and Denenberg, 1999;Gibbs, 2000;Dohan...

show abstract

The Development of Casodex™ (Bicalutamide): Preclinical Studies

Cited by 68 publications

References 34 publications

Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides

Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides

Androgen receptor antagonists for prostate cancer therapy

A randomized controlled trial of add-back estrogen or placebo on cognition in men with prostate cancer receiving an antiandrogen and a gonadotropin-releasing hormone analog

Contact Info

Product

Resources

About