From Wikipedia, the free encyclopedia
Jump to: navigation, search
Bicalutamide (INN, USAN, BAN)
Bicalutamide ball-and-stick.png
Systematic (IUPAC) name
Clinical data
Trade names Casodex
AHFS/ monograph
MedlinePlus a697047
  • US: X (Contraindicated)
Legal status
  • (Prescription only)
Routes of
Pharmacokinetic data
Bioavailability Well-absorbed
Protein binding 96%
Metabolism Hepatic (CYP3A4)
Biological half-life 6 days (acute),[1]
7–10 days (chronic)[2]
CAS Number 90357-06-5 YesY
ATC code L02BB03
PubChem CID 2375
DrugBank DB01128 YesY
ChemSpider 2284 YesY
KEGG D00961 N
Synonyms ICI-176334[3]
PDB ligand ID 198 (PDBe, RCSB PDB)
Chemical data
Formula C18H14F4N2O4S
Molar mass 430.373 g/mol
 NYesY (what is this?)  (verify)

Bicalutamide (brand names Casodex, Cosudex, Calutide, Kalumid) is a synthetic, non-steroidal, pure antiandrogen used in the treatment of prostate cancer,[4][5][6] hirsutism,[7][8] and other androgen-dependent conditions.[3][9][10] Developed and marketed by AstraZeneca,[11] bicalutamide was approved in 1995 as a combination treatment (with a gonadotropin-releasing hormone (GnRH) analogue (e.g., leuprorelin) or surgical castration)[12][13] for stage D2 metastatic prostate cancer, and has since also been approved and used, for instance in Germany, as a monotherapy for the treatment of an earlier stage of the disease, stage C or D1 locally advanced prostate cancer.[14] Prior to the approval of enzalutamide, a recently introduced, newer non-steroidal antiandrogen with improved effectiveness, bicalutamide was regarded as the standard-of-care antiandrogen for the treatment of prostate cancer.[15]

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[16]

Medical uses[edit]

Prostate cancer[edit]

Bicalutamide is indicated for the treatment of stage D2 metastatic prostate cancer in combination with castration (pharmacological with a GnRH analogue or surgical with an orchiectomy)[17] or as a monotherapy.[18] However, while effective, most advanced prostate cancer patients eventually become resistant to antiandrogen including bicalutamide therapy, due to progressive mutations in the androgen receptor (AR) resulting in the transformation of these drugs from antagonists into agonists of the AR.[19]

Other/off-label uses[edit]

Bicalutamide, along with other non-steroidal antiandrogens including flutamide and nilutamide, is used as a component of hormone replacement therapy for trans women.[20][21] However, relative to flutamide and nilutamide, bicalutamide is, in general, clinically preferred due to its superior safety, tolerability, and pharmacokinetic profiles (see below).[22][23]

Low-dose (25 mg/day) bicalutamide has been found to be effective in the treatment of hirsutism in women.[7][8][24]

Bicalutamide is useful in combination with the aromatase inhibitor anastrozole as a puberty blocker in the treatment of precocious puberty in boys.[25][26] This is a cost-effective alternative to GnRH analogues for the treatment of this condition. Moreover, the combination is effective in gonadotropin-independent precocious puberty in boys, such as in familial male-limited precocious puberty (a.k.a. testotoxicosis), where GnRH analogues are not effective.[25][26]

Side effects[edit]

Known potential side effects of bicalutamide, many of which may be exclusive to males, include breast pain/tenderness, gynecomastia, hot flashes, depression, fatigue, sexual dysfunction (including loss of libido and erectile dysfunction),[27] diarrhea, nausea, pruritus (itching), and, rarely, hepatic changes (e.g., transiently elevated levels of transaminases, jaundice[28]).[29][30][31][32]

Some of the above-listed side effects, including breast pain/tenderness and gynecomastia, are far less likely to occur when bicalutamide is combined with a GnRH analogue (due to suppression of estrogen levels),[33] and others, including hot flashes, depression, fatigue, and loss of libido,[34] may occur much more often when bicalutamide is combined with a GnRH analogue.[35][36][37] It has been hypothesized that this is due to the suppression of both androgen and estrogen levels by GnRH analogues, as estrogen may be able to compensate for various negative central effects of androgen deprivation, while bicalutamide monotherapy, contrarily, increases estrogen levels.[35]

Tamoxifen, a selective estrogen receptor modulator, has been found to be highly effective in preventing and reversing bicalutamide-induced gynecomastia in men with prostate cancer.[38][39] For reasons that are unclear, anastrozole, an aromatase inhibitor, has been found to be much less effective in comparison to tamoxifen for this indication.[38][39] A systematic review of non-steroidal antiandrogen-induced gynecomastia and mastodynia concluded that tamoxifen, 10–20 mg/day, and radiotherapy could effectively manage the condition without relevant side effects, with tamoxifen showing superior effectiveness.[40]

In accordance with its antiandrogen properties, bicalutamide reduces the weight of the prostate gland and seminal vesicles,[41] though not the testes.[42] As such, it may produce hypospermia or aspermia (reduced or absent semen/ejaculate production),[43] an often-observed effect of antiandrogen therapy for prostate cancer.[44] However, in spite of this, bicalutamide, conversely, does not appear to adversely affect spermatogenesis, and thus may not necessarily abolish fertility.[42]

From a theoretical standpoint, flutamide, nilutamide, and bicalutamide are all thought to be capable of causing hepatotoxicity,[45][46] However, relative to flutamide (which has an estimated incidence rate of 3 in every 10,000, or 0.0003%), hepatotoxicity is much rarer in nilutamide and bicalutamide, and the risk is thought to be significantly less with nilutamide and even further less with bicalutamide.[2][46][47] A total of four cases of bicalutamide-associated hepatotoxicity have been reported in the medical literature.[28]

A few cases of interstitial pneumonitis in association with bicalutamide treatment have been reported in the medical literature[48][49][50] Incidence is very rare, and the risk of interstitial pneumonitis is far less relative to that seen with nilutamide.[49]

All of the approved non-steroidal antiandrogens, flutamide, nilutamide, bicalutamide, and enzalutamide, have been found to possess an off-target action of inhibiting GABAA receptor currents in vitro to varying extents.[51] In addition, flutamide, nilutamide, and enzalutamide have been found to cause convulsions and/or death in mice at sufficient doses.[51] Bicalutamide was not found to do this, but this may have simply been due to the limited brain penetration of bicalutamide in rodents.[51] In any case, regardless of animal findings, enzalutamide is the only non-steroidal antiandrogen that has been found to be associated with a significantly increased incidence of seizures clinically, so the relevance of aforementioned findings with regard to the other agents is unclear.[51]


Due to its actions as an antiandrogen, bicalutamide is a teratogen and should not be taken or handled by women who are or who may become pregnant.[52][53] It is known to have the potential to cause fetal defects, such as ambiguous genitalia.[52][53]

In individuals with severe, though not mild-to-moderate hepatic impairment, there is evidence that the elimination of bicalutamide is slowed, and hence, it should be used cautiously in these patients.[54][55]

Comparison with other antiandrogens[edit]

Relative to the non-steroidal antiandrogens flutamide and nilutamide, bicalutamide has the highest affinity for the AR (e.g., 4-fold greater than flutamide),[27] as well as the longest half-life (~6 days for bicalutamide versus 5–6 hours for flutamide and ~2 days for nilutamide).[22] Bicalutamide is described as the most potent of the non-steroidal antiandrogens as well as the most well-tolerated (not including/considering enzalutamide).[1] It is for these reasons, as well as a better safety profile, that bicalutamide has largely replaced flutamide and nilutamide in the treatment of prostate cancer.[45]

In comparison to bicaclutamide, the newer non-steroidal antiandrogen enzalutamide has 5- to 8-fold higher affinity for the AR,[56][57] possesses mechanistic differences resulting in improved AR deactivation,[56][58] shows increased (though by no means complete) resistance to AR mutations in prostate cancer cells causing a switch from antagonist to agonist activity,[56][59] and has a slightly longer half-life (8–9 days versus ~6 days).[60] In accordance, enzalutamide appears to be a much more potent antiandrogen relative to bicalutamide (for instance, producing substantially greater increases in testosterone levels relative to bicalutamide at similar dosages (114% for enzalutamide 160 mg/day relative to 66% for bicalutamide 150 mg/day), and similar increases (with the 160 mg/day dosage) in testosterone, estradiol, and luteinizing hormone (LH) levels relative to high-dosage bicalutamide (300–600 mg/day)),[61][62] and the drug has demonstrated superior effectiveness in comparison to bicalutamide in the treatment of prostate cancer.[63] In terms of tolerability, enzalutamide and bicalutamide appear overall to be similar,[citation needed] with a similar moderate negative effect on sexual function and activity, for instance.[62] However, enzalutamide has a risk of seizures and other side effects such as anxiety and insomnia related to off-target GABAA receptor inhibition that bicalutamide does not appear to have.[51][60] Also, unlike bicalutamide, enzalutamide is still on-patent, and for this reason, is extremely expensive ($7,450 USD for a 30-day supply as of 2015).[64] Contrarily, the cost of bicalutamide is very low in comparison (from $15.44 for a 30-day supply of once-daily 50 mg tablets).[65]

In clinical studies, flutamide has been found to be more effective than both spironolactone and cyproterone acetate in the treatment of androgen-dependent conditions such as acne and hirsutism in women.[66][67][68] Bicalutamide has similarly been tried and found to be effective in the treatment of hirsutism in women.[7][8][24] However, although it has not been compared head-to-head with other antiandrogens in any trials for such conditions, relative to flutamide, as mentioned above, bicalutamide is several times more potent and has a much longer half-life, and hence would be expected to be at least equivalent or perhaps even more effective in comparison.[22][27] In accordance with this notion, the efficacy of bicalutamide has been found to be at least equivalent to flutamide in the treatment of prostate cancer in a direct head-to-head comparison, and indications of superior efficacy, including significantly greater relative decreases and increases in levels of prostate-specific antigen (PSA) and testosterone, respectively, were observed.[69][70]

It is noteworthy that monotherapy with non-steroidal, pure antiandrogens including flutamide and bicalutamide significantly increases androgen and estrogen levels in men, but that this does not occur in women.[71][72][73] As such, bicalutamide on its own may be significantly more effective as an antiandrogen in women relative to men. However, monotherapy with higher dosages of bicalutamide (150 mg/day) has still been found to be clinically effective in the treatment of prostate cancer in men, and thus as an antiandrogen.[14]



Bicalutamide acts as a potent and highly selective competitive silent antagonist of the androgen receptor (AR). This prevents the activation of the AR and subsequent upregulation of androgen-responsive genes by androgens such as testosterone and dihydrotestosterone (DHT).[41][74] Bicalutamide has also notably been found to accelerate the degradation of the AR.[75] Owing to its selectivity, unlike steroidal antiandrogens such as cyproterone acetate and megestrol acetate,[76] bicalutamide does not additionally inhibit or suppress androgen production in the body – instead, it exclusively blocks androgen binding and subsequent receptor activation at the level of the AR.[77]

Based on animal research, it was initially thought that bicalutamide was unable to cross the blood-brain-barrier and hence was a peripherally-selective antiandrogen.[41][69] This conclusion was drawn from the finding that bicalutamide does not increase luteinizing hormone (LH) or testosterone levels in animals (including in rats and dogs),[41][69][78][79] as antiandrogens like flutamide normally do this by blocking ARs in the hypothalamus and pituitary gland and thereby disinhibiting the hypothalamic-pituitary-gonadal (HPG) axis.[35] In humans however, bicalutamide has been found to increase LH and testosterone levels, and to a comparative extent relative to flutamide and nilutamide.[35][54][69][80][81] As such, it appears that bicalutamide does indeed cross the blood-brain-barrier in humans and affect central function, as supported by potential side effects such as diminished sexual interest, fatigue, and depression.[34] It has since been hypothesized that this difference of bicalutamide in animals and humans may be due to species-related differences in drug tissue distribution.[54][81]

As touched on above, blockade of the AR by bicalutamide in the hypothalamus and pituitary gland suppresses the negative feedback of androgens on the release of LH.[35] This, in turn, leads to a significant increase in androgen and estrogen levels.[82] Bicalutamide will more than block the effects of the increased androgen levels (in demonstration, monotherapy is still clinically effective in the treatment of prostate cancer),[14] but the effect of the elevated estrogen levels will remain unopposed and lead to feminizing effects, most notably gynecomastia.[83]

If bicalutamide is combined with a GnRH analogue or surgical castration, the elevation of androgen and estrogen levels will be prevented and the risks of excessive estrogens, such as gynecomastia, will be reduced.[33] However, since both androgens and estrogens are essential for normal bone metabolism, reducing the anabolic bone effects of both androgens (which increase bone formation by stimulating osteoblasts)[84] and estrogens (which reduce bone resorption by inhibiting osteoclasts)[85] will increase bone loss and promote osteoporosis.[86] In addition, hot flashes, depression, fatigue, and loss of libido are much more likely to occur when bicalutamide is combined with a GnRH analogue.[36][37] It has been proposed that this, including maintenance of mood and sexual interest, may be due to estrogen compensating for the decreased androgen activity in the brain.

Non-steroidal antiandrogens including bicalutamide, flutamide, nilutamide, and enzalutamide show a significantly lower risk of certain side effects, including hot flashes, depression, fatigue, loss of libido, and decreased sexual activity, relative to treatment with GnRH analogues, maximal androgen blockade (MAB), cyproterone acetate, or surgical castration in prostate cancer.[5][35][87][88] For example, 60% of men reported complete loss of libido with bicalutamide relative to 85% for MAB and 69% reported complete loss of erectile function relative to 93% for MAB.[5] Another large study reported a rate of impotence of only 9.3% with bicalutamide relative to 6.5% for standard care (the controls), a rate of decreased libido of only 3.6% with bicalutamide relative to 1.2% for standard care, and a rate of 9.2% with bicalutamide for hot flashes relative to 5.4% for standard care.[89] One other study reported decreased libido, impotence, and hot flashes in only 3.8%, 16.9%, and 3.1% of bicalutamide-treated patients, respectively, relative to 1.3%, 7.1%, and 3.6% for placebo.[90]

It has been proposed that the increase in estrogen levels caused by non-steroidal antiandrogens compensates for the androgen blockade in the brain, which may explain the above-described difference (as GnRH analogues, MAB, and cyproterone acetate, contrarily, decrease both androgen and estrogen levels).[87][88][91] In regards to sexual interest and function, this idea is supported by a variety of findings, including animal studies showing that estrogen deficiency results in impaired sexual behavior, that treatment with tamoxifen results in significantly lowered libido in 30% of men being treated with it for male breast cancer, and that in men with congenital estrogen deficiency, estrogen administration restores libido and the frequency of sexual intercourse, among others.[87][88][91] It has been proposed that due to the lower relative effect of non-steroidal antiandrogens including bicalutamide and flutamide on sexual interest and activity, with two-thirds of advanced or metastatic prostate cancer patients treated with non-steroidal antiandrogens retaining sexual interest, these agents may be preferable and result in improved quality of life for those who wish to retain sexual interest and function relative to other antiandrogen therapies in prostate cancer.[35]

Several metabolites of testosterone and DHT, including estradiol, 3α-androstanediol, and 3β-androstanediol, are potent estrogens, and 3β-androstanediol is also a potent GABAA receptor-potentiating neurosteroid.[92][93] Due to the fact that bicalutamide does not lower androgen levels, the levels of these androgen metabolites are likely not lowered either, unlike with therapies such as GnRH analogues. These steroids have been found to have AR-independent positive effects on sexual motivation,[92][93][94] and may explain the preservation of sexual interest and function by bicalutamide and other non-steroidal antiandrogens. They also have antidepressant and anxiolytic effects,[95][96][97] and may account for the lower incidence of depression with bicalutamide and other non-steroidal antiandrogens relative to other therapies.

Unlike with antigonadotropic antiandrogens such as cyproterone acetate, spironolactone, and GnRH analogues, it has been reported that bicalutamide monotherapy (at 50 mg/day) has very little effect on the ultrastructure of the testes and on sperm maturation even after long-term therapy (>4 years).[42] This may be explained by the fact that testosterone levels are far higher in the testes than in the rest of the body (concentrations in the seminiferous tubules are 20- to 100-fold greater than circulating levels, to demonstrate),[98] and systemic bicalutamide therapy is likely unable to result in intratesticular concentrations of the drug that are able to significantly block androgen action in this part of the body due to the higher androgen levels that are present.[42] This is especially so considering that bicalutamide increases circulating testosterone levels and by extension gonadal testosterone production by up to two-fold in males.[82] In contrast to bicalutamide and other pure/non-steroidal antiandrogens, antigonadotropic antiandrogens suppress gonadotropin secretion, which in turn suppresses testosterone production by the testes as well as other gonadotropin effects on the testes. As such, bicalutamide and other non-steroidal antiandrogens may uniquely preserve testicular function and spermatogenesis and thus male fertility.[42][99]

The activity of bicalutamide lies in the R-isomer, which binds to the AR with an affinity that is about 30-fold higher than that of the S-isomer.[77] The active R-isomer also has a much longer half-life than the S-isomer.[77] At steady-state, serum levels of (R)-bicalutamide are about 100-fold greater than those of (S)-bicalutamide.[100]

Though a pure antagonist of the AR under normal circumstances, bicalutamide, as well as other earlier antiandrogens, have been found to possess partial agonist properties in the setting of AR overexpression or certain mutations in the ligand-binding domain (LBD) of the AR.[101] As both of these circumstances can eventually occur in prostate cancer, resistance to bicalutamide usually develops and the drug has the potential to paradoxically stimulate tumor growth when this happens.[101][102] This is the mechanism of the phenomenon of antiandrogen withdrawal syndrome.[102] The newer drug, enzalutamide, does not have agonistic properties in the context of overexpression of the AR, though certain mutations in the AR can still convert it from an antagonist to agonist.[101]

Other actions[edit]

Bicalutamide, as well as enzalutamide, have been found to act as inhibitors of ABCB1 (P-glycoprotein) efflux and ATPase activity.[103][104][105] This action may reverse docetaxel resistance in prostate cancer cells by reducing transport of the drug out of these cells.[103][104][105]

Bicalutamide has been identified as a strong CYP27A1 inhibitor in vitro.[106] CYP27A1 converts cholesterol into 27-hydroxycholesterol, an oxysterol that has multiple biological functions, including direct, tissue-specific activation of the estrogen receptor (ER) (it has been characterized as a selective estrogen receptor modulator) and the liver X receptor.[106] 27-Hydroxycholesterol has been found to increase ER-positive breast cancer cell growth via its estrogenic action, and hence, it has been proposed that bicalutamide and other CYP27A1 inhibitors may be effective as adjuvant therapies to aromatase inhibitors in the treatment of ER-positive breast cancer.[106]


Dosage and absorption[edit]

Bicalutamide is used in dosages of 50 mg/day in combination with a GnRH analogue in the treatment of prostate cancer and at a dosage of 150 mg/day as a monotherapy for prostate cancer.[1] Bicalutamide has been found to be ineffective as a monotherapy in prostate cancer at a dosage of 50 mg/day.[63]

Bicalutamide has been used at a dosage of 25 mg/day in the treatment of hirsutism in women.[7][8][24]

Dosages of bicalutamide of 300 mg, 450 mg, and 600 mg per day all give similar plasma levels of the drug, indicating a saturation of absorption.[107] At a 300 mg per day dosage, plasma levels are about 50% higher relative to 150 mg per day, while plasma levels are only about 15% higher relative to 200 mg per day.[107] As such, plasma levels of bicalutamide reach a plateau at 300 mg per day, with higher dosages being ineffective in raising plasma levels further.[107] In accordance, the effectiveness, tolerability, and toxicity of 150 mg, 300 mg, 450 mg, and 600 mg per day dosages of bicalutamide are all similar.[107] However, there is some evidence of greater effectiveness of 300 mg per day (and the equivalent 450 mg and 600 mg dosages) relative to 150 mg per day in the treatment of prostate cancer.[107]

Dosages of bicalutamide of 10 mg, 30 mg, and 50 mg per day have been found to produce a moderate effect on sex hormone levels in men with prostate cancer, indicating that the drug has clinically-relevant antiandrogen effects at a dosage as low as 10 mg/day in males.[108]

Duration and metabolism[edit]

Bicalutamide has a very long serum half-life of about 6 days with a single dose,[1] and a half-life of 7–10 days with repeated administration, allowing for once-daily dosing.[2]

Bicalutamide is almost exclusively metabolized by the enzyme CYP3A4.[54][100]

It has been reported that bicalutamide may have the potential to inhibit the enzymes CYP3A4 and, to a lesser extent, CYP2C9, CYP2C19, and CYP2D6, based on in vitro research.[54] However, no relevant inhibition of CYP3A4 has been observed in vivo with bicalutamide at a dose of 150 mg (using midazolam as a specific marker of CYP3A4).[54] In animals, bicalutamide has been found to be an inducer of certain cytochrome P450 enzymes.[54] However, dosages of 150 mg/day or less have shown no evidence of this in humans.[54]


Bicalutamide has been tested with good results for the treatment of AR-positive ER/PR-negative locally advanced and metastatic breast cancer in a phase II study and has been used off-label for this indication.[109][110][111] The newer non-steroidal antiandrogen enzalutamide may also hold some promise for this type of cancer but has been so far tested only in vitro.[citation needed]

Bicalutamide has been researched in clinical trials for ovarian cancer, with effectiveness observed.[112]

See also[edit]


  1. ^ a b c d Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2939–. ISBN 978-1-4160-6911-9. 
  2. ^ a b c Jordan VC, Furr BJ (5 February 2010). Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 350–. ISBN 978-1-59259-152-7. 
  3. ^ a b Morton IK, Hal JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 51–. ISBN 978-94-011-4439-1. 
  4. ^ Schellhammer PF (Sep 2002). "An evaluation of bicalutamide in the treatment of prostate cancer". Expert Opinion on Pharmacotherapy 3 (9): 1313–28. doi:10.1517/14656566.3.9.1313. PMID 12186624. 
  5. ^ a b c Fradet Y (Feb 2004). "Bicalutamide (Casodex) in the treatment of prostate cancer". Expert Review of Anticancer Therapy 4 (1): 37–48. doi:10.1586/14737140.4.1.37. PMID 14748655. 
  6. ^ See WA, Tyrrell CJ (Aug 2006). "The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer". Journal of Cancer Research and Clinical Oncology. 132 Suppl 1: S7–16. doi:10.1007/s00432-006-0132-6. PMID 16896884. 
  7. ^ a b c d Erem C (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clinica Belgica 68 (4): 268–74. doi:10.2143/ACB.3267. PMID 24455796. 
  8. ^ a b c d Müderris II, Bayram F, Ozçelik B, Güven M (Feb 2002). "New alternative treatment in hirsutism: bicalutamide 25 mg/day". Gynecological Endocrinology 16 (1): 63–6. doi:10.1080/713602986. PMID 11915584. 
  9. ^ Swiss Pharmaceutical Society, ed. (January 2000). Index Nominum 2000: International Drug Directory. Taylor & Francis. pp. 123–. ISBN 978-3-88763-075-1. 
  10. ^ Ganellin CR, Triggle DJ (21 November 1996). Dictionary of Pharmacological Agents. CRC Press. pp. 570–. ISBN 978-0-412-46630-4. 
  11. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Elsevier. pp. 627–. ISBN 978-0-8155-1856-3. 
  12. ^ Klotz L (May 2006). "Combined androgen blockade: an update". The Urologic Clinics of North America 33 (2): 161–6, v–vi. doi:10.1016/j.ucl.2005.12.001. PMID 16631454. 
  13. ^ Wellington K, Keam SJ (2006). "Bicalutamide 150mg: a review of its use in the treatment of locally advanced prostate cancer". Drugs 66 (6): 837–50. doi:10.2165/00003495-200666060-00007. PMID 16706554. 
  14. ^ a b c Wass JA, Stewart PM (28 July 2011). Oxford Textbook of Endocrinology and Diabetes. OUP Oxford. pp. 1625–. ISBN 978-0-19-923529-2. 
  15. ^ Regitz-Zagrosek V (2 October 2012). Sex and Gender Differences in Pharmacology. Springer Science & Business Media. pp. 575–. ISBN 978-3-642-30725-6. 
  16. ^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015. 
  17. ^ Klotz L, Schellhammer P (Mar 2005). "Combined androgen blockade: the case for bicalutamide". Clinical Prostate Cancer 3 (4): 215–9. doi:10.3816/cgc.2005.n.002. PMID 15882477. 
  18. ^ Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ (Sep 1997). "Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group". Urology 50 (3): 330–6. doi:10.1016/S0090-4295(97)00279-3. PMID 9301693. 
  19. ^ Balk SP (Sep 2002). "Androgen receptor as a target in androgen-independent prostate cancer". Urology 60 (3 Suppl 1): 132–8; discussion 138–9. doi:10.1016/S0090-4295(02)01593-5. PMID 12231070. 
  20. ^ Bockting W, Coleman E, De Cuypere G (Jun 2011). "Care of transsexual persons". The New England Journal of Medicine 364 (26): 2559–60; author reply 2560. doi:10.1056/NEJMcp1008161. PMID 21714669. 
  21. ^ Ho CK (Dec 2011). "Testosterone testing in adult males". The Malaysian Journal of Pathology 33 (2): 71–81. PMID 22299206. 
  22. ^ a b c Gulley JL (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–. ISBN 978-1-935281-91-7. 
  23. ^ Moser L (1 January 2008). Controversies in the Treatment of Prostate Cancer. Karger Medical and Scientific Publishers. pp. 41–42. ISBN 978-3-8055-8524-8. 
  24. ^ a b c Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B (22 January 2009). Evidence-Based Dermatology. John Wiley & Sons. pp. 529–. ISBN 978-1-4443-0017-8. 
  25. ^ a b Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z (Sep 2006). "Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole". The Journal of Pediatrics 149 (3): 416–20. doi:10.1016/j.jpeds.2006.04.027. PMID 16939760. 
  26. ^ a b Reiter EO, Mauras N, McCormick K, Kulshreshtha B, Amrhein J, De Luca F, O'Brien S, Armstrong J, Melezinkova H (Oct 2010). "Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT)". Journal of Pediatric Endocrinology & Metabolism 23 (10): 999–1009. doi:10.1515/jpem.2010.161. PMID 21158211. 
  27. ^ a b c Resnick MI, Thompson IM (2000). Advanced Therapy of Prostate Disease. PMPH-USA. pp. 379–. ISBN 978-1-55009-102-1. 
  28. ^ a b Hussain S, Haidar A, Bloom RE, Zayouna N, Piper MH, Jafri SM (2014). "Bicalutamide-induced hepatotoxicity: A rare adverse effect". The American Journal of Case Reports 15: 266–70. doi:10.12659/AJCR.890679. PMID 24967002. 
  29. ^ Lunglmayr G (Aug 1995). "Efficacy and tolerability of Casodex in patients with advanced prostate cancer. International Casodex Study Group". Anti-Cancer Drugs 6 (4): 508–13. doi:10.1097/00001813-199508000-00003. PMID 7579554. 
  30. ^ McLeod DG (1997). "Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer". The Oncologist 2 (1): 18–27. PMID 10388026. 
  31. ^ Dart RC (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 521–. ISBN 978-0-7817-2845-4. 
  32. ^ DeAngelis LM, Posner JB (12 September 2008). Neurologic Complications of Cancer. Oxford University Press, USA. pp. 479–. ISBN 978-0-19-971055-3. 
  33. ^ a b Droz JP, Audisio RA (2 October 2012). Management of Urological Cancers in Older People. Springer Science & Business Media. pp. 84–. ISBN 978-0-85729-986-4. 
  34. ^ a b Mason M (Aug 2006). "What implications do the tolerability profiles of antiandrogens and other commonly used prostate cancer treatments have on patient care?". Journal of Cancer Research and Clinical Oncology. 132 Suppl 1: S27–35. doi:10.1007/s00432-006-0134-4. PMID 16896883. 
  35. ^ a b c d e f g Iversen P, Melezinek I, Schmidt A (Jan 2001). "Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function". BJU International 87 (1): 47–56. doi:10.1046/j.1464-410x.2001.00988.x. PMID 11121992. 
  36. ^ a b Cher ML, Honn KV, Raz A (11 April 2006). Prostate Cancer: New Horizons in Research and Treatment. Springer Science & Business Media. pp. 382–. ISBN 978-0-306-48143-7. 
  37. ^ a b Feldman D, Marcus R, Nelson D, Rosen CJ (8 November 2007). Osteoporosis. Academic Press. pp. 1354–. ISBN 978-0-08-055347-4. 
  38. ^ a b Saltzstein D, Sieber P, Morris T, Gallo J (2005). "Prevention and management of bicalutamide-induced gynecomastia and breast pain: randomized endocrinologic and clinical studies with tamoxifen and anastrozole". Prostate Cancer and Prostatic Diseases 8 (1): 75–83. doi:10.1038/sj.pcan.4500782. PMID 15685254. 
  39. ^ a b Boccardo F, Rubagotti A, Battaglia M, Di Tonno P, Selvaggi FP, Conti G, Comeri G, Bertaccini A, Martorana G, Galassi P, Zattoni F, Macchiarella A, Siragusa A, Muscas G, Durand F, Potenzoni D, Manganelli A, Ferraris V, Montefiore F (Feb 2005). "Evaluation of Tamoxifen and Anastrozole in the Prevention of Gynecomastia and Breast Pain Induced by Bicalutamide Monotherapy of Prostate Cancer". J Clin Oncol 23: 808–15. doi:10.1200/JCO.2005.12.013. PMID 15681525. 
  40. ^ Fagerlund A, Cormio L, Palangi L, Lewin R, Santanelli di Pompeo F, Elander A, Selvaggi G (2015). "Gynecomastia in Patients with Prostate Cancer: A Systematic Review". PLOS ONE 10 (8): e0136094. doi:10.1371/journal.pone.0136094. PMID 26308532. 
  41. ^ a b c d Furr BJ, Tucker H (Jan 1996). "The preclinical development of bicalutamide: pharmacodynamics and mechanism of action". Urology 47 (1A Suppl): 13–25; discussion 29–32. doi:10.1016/S0090-4295(96)80003-3. PMID 8560673. 
  42. ^ a b c d e Morgante, E; Gradini, R; Realacci, M; Sale, P; D'eramo, G; Perrone, G A; Cardillo, M R; Petrangeli, E; Russo, Ma; Di Silverio, F (2001). "Effects of long-term treatment with the anti-androgen bicalutamide on human testis: an ultrastructural and morphometric study". Histopathology 38 (3): 195–201. doi:10.1046/j.1365-2559.2001.01077.x. ISSN 0309-0167. 
  43. ^ Mazzola, Clarisse R; Mulhall, John P (2012). "Impact of androgen deprivation therapy on sexual function". Asian Journal of Andrology 14 (2): 198–203. doi:10.1038/aja.2011.106. ISSN 1008-682X. 
  44. ^ John J. Mulcahy (1 January 2001). Male Sexual Function. Springer Science & Business Media. pp. 3–. ISBN 978-1-59259-098-8. 
  45. ^ a b Bunce CM, Campbell MJ (11 March 2010). Nuclear Receptors: Current Concepts and Future Challenges. Springer Science & Business Media. pp. 160–. ISBN 978-90-481-3303-1. 
  46. ^ a b Dansette P, Snyder RR, Monks TJ, Jollow DJ, Sipes IG, Greim H, Gibson GG, Delaforge M (6 December 2012). Biological Reactive Intermediates Vi: Chemical and Biological Mechanisms in Susceptibility to and Prevention of Environmental Diseases. Springer Science & Business Media. pp. 37–. ISBN 978-1-4615-0667-6. 
  47. ^ Ramon J, Denis LJ (5 June 2007). Prostate Cancer. Springer Science & Business Media. pp. 256–. ISBN 978-3-540-40901-4. 
  48. ^ Dart RC (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 497–. ISBN 978-0-7817-2845-4. 
  49. ^ a b Masago T, Watanabe T, Nemoto R, Motoda K (Dec 2011). "Interstitial pneumonitis induced by bicalutamide given for prostate cancer". International Journal of Clinical Oncology 16 (6): 763–5. doi:10.1007/s10147-011-0239-x. PMID 21537882. 
  50. ^ Aronson JK (4 March 2014). Side Effects of Drugs Annual: A worldwide yearly survey of new data in adverse drug reactions. Newnes. pp. 740–. ISBN 978-0-444-62636-3. 
  51. ^ a b c d e Foster WR, Car BD, Shi H, Levesque PC, Obermeier MT, Gan J, Arezzo JC, Powlin SS, Dinchuk JE, Balog A, Salvati ME, Attar RM, Gottardis MM (Apr 2011). "Drug safety is a barrier to the discovery and development of new androgen receptor antagonists". The Prostate 71 (5): 480–8. doi:10.1002/pros.21263. PMID 20878947. 
  52. ^ a b Iswaran TJ, Imai M, Betton GR, Siddall RA (May 1997). "An overview of animal toxicology studies with bicalutamide (ICI 176,334)". The Journal of Toxicological Sciences 22 (2): 75–88. doi:10.2131/jts.22.2_75. PMID 9198005. 
  53. ^ a b Smith RE (4 April 2013). Medicinal Chemistry - Fusion of Traditional and Western Medicine. Bentham Science Publishers. pp. 306–. ISBN 978-1-60805-149-6. 
  54. ^ a b c d e f g h Cockshott ID (2004). "Bicalutamide: clinical pharmacokinetics and metabolism". Clinical Pharmacokinetics 43 (13): 855–78. doi:10.2165/00003088-200443130-00003. PMID 15509184. 
  55. ^ Skeel RT, Khleif SN (2011). Handbook of Cancer Chemotherapy. Lippincott Williams & Wilkins. pp. 724–. 
  56. ^ a b c Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (May 2009). "Development of a second-generation antiandrogen for treatment of advanced prostate cancer". Science 324 (5928): 787–90. doi:10.1126/science.1168175. PMC 2981508. PMID 19359544. 
  57. ^ Rodriguez-Vida A, Galazi M, Rudman S, Chowdhury S, Sternberg CN (2015). "Enzalutamide for the treatment of metastatic castration-resistant prostate cancer". Drug Design, Development and Therapy 9: 3325–39. doi:10.2147/DDDT.S69433. PMID 26170619. 
  58. ^ Antonarakis ES (Jun 2013). "Enzalutamide: The emperor of all anti-androgens". Translational Andrology and Urology 2 (2): 119–120. PMC 3785324. PMID 24076589. 
  59. ^ Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, Brigham D, Moon M, Maneval EC, Chen I, Darimont B, Hager JH (Sep 2013). "A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509". Cancer Discovery 3 (9): 1020–9. doi:10.1158/2159-8290.CD-13-0226. PMID 23779130. 
  60. ^ a b Litt JZ (25 January 2013). Litt's Drug Eruptions and Reactions Manual, 19th Edition. CRC Press. pp. 148–. ISBN 978-1-84214-599-9. 
  61. ^ Ricci F, Buzzatti G, Rubagotti A, Boccardo F (Nov 2014). "Safety of antiandrogen therapy for treating prostate cancer". Expert Opinion on Drug Safety 13 (11): 1483–99. doi:10.1517/14740338.2014.966686. PMID 25270521. 
  62. ^ a b Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR (May 2014). "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study". The Lancet. Oncology 15 (6): 592–600. doi:10.1016/S1470-2045(14)70129-9. PMID 24739897. 
  63. ^ a b Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Baron B, Hirmand M, Smith MR (Feb 2015). "Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results". European Urology. doi:10.1016/j.eururo.2015.01.027. PMID 25687533. 
  64. ^ Ramadan WH, Kabbara WK, Al Basiouni Al Masri HS (2015). "Enzalutamide for patients with metastatic castration-resistant prostate cancer". OncoTargets and Therapy 8: 871–6. doi:10.2147/OTT.S80488. PMID 25945058. 
  65. ^ "Bicalutamide Prices, Coupons and Patient Assistance Programs". Retrieved 31 August 2015. 
  66. ^ Haber RS, Stough DB (2006). Hair Transplantation. Elsevier Health Sciences. p. 6. ISBN 978-1-4160-3104-8. Retrieved 28 May 2012. 
  67. ^ Goroll AH, Mulley AG (27 January 2009). Primary Care Medicine: Office Evaluation and Management of the Adult Patient. Lippincott Williams & Wilkins. p. 1264. ISBN 978-0-7817-7513-7. Retrieved 28 May 2012. 
  68. ^ Grigoriou O, Papadias C, Konidaris S, Antoniou G, Karakitsos P, Giannikos L (Apr 1996). "Comparison of flutamide and cyproterone acetate in the treatment of hirsutism: a randomized controlled trial". Gynecological Endocrinology 10 (2): 119–23. doi:10.3109/09513599609097901. PMID 8701785. 
  69. ^ a b c d Helsen C, Van den Broeck T, Voet A, Prekovic S, Van Poppel H, Joniau S, Claessens F (Aug 2014). "Androgen receptor antagonists for prostate cancer therapy". Endocrine-Related Cancer 21 (4): T105–18. doi:10.1530/ERC-13-0545. PMID 24639562. 
  70. ^ Nakai Y, Tanaka N, Anai S, Miyake M, Tatsumi Y, Fujimoto K (2015). "A Randomized Control Trial Comparing the Efficacy of Antiandrogen Monotherapy: Flutamide vs. Bicalutamide". Horm Cancer 6 (4): 161–7. doi:10.1007/s12672-015-0226-1. PMID 26024831. 
  71. ^ Diamanti-Kandarakis E, Nestler JE, Panidis D, Pasquali R (21 December 2009). Insulin Resistance and Polycystic Ovarian Syndrome: Pathogenesis, Evaluation, and Treatment. Springer Science & Business Media. pp. 75–. ISBN 978-1-59745-310-3. 
  72. ^ Carrell DT, Peterson CM (23 March 2010). Reproductive Endocrinology and Infertility: Integrating Modern Clinical and Laboratory Practice. Springer Science & Business Media. pp. 163–. ISBN 978-1-4419-1436-1. 
  73. ^ Journal of Reproductive Medicine. Journal of Reproductive Medicine, Incorporated. July 1994. 
  74. ^ Furr BJ (1996). "The development of Casodex (bicalutamide): preclinical studies". European Urology. 29 Suppl 2: 83–95. PMID 8717469. 
  75. ^ Waller AS, Sharrard RM, Berthon P, Maitland NJ (Jun 2000). "Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, casodex". Journal of Molecular Endocrinology 24 (3): 339–51. doi:10.1677/jme.0.0240339. PMID 10828827. 
  76. ^ Chang C (1 January 2005). Prostate Cancer: Basic Mechanisms and Therapeutic Approaches. World Scientific. pp. 11–. ISBN 978-981-256-920-2. 
  77. ^ a b c Schellens JH, McLeod HL, Newell DR (5 May 2005). Cancer Clinical Pharmacology. OUP Oxford. pp. 229–. ISBN 978-0-19-262966-1. 
  78. ^ Furr BJ (1989). ""Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies". Hormone Research. 32 Suppl 1 (1): 69–76. doi:10.1159/000181315. PMID 2533159. 
  79. ^ Furr BJ, Valcaccia B, Curry B, Woodburn JR, Chesterson G, Tucker H (Jun 1987). "ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen". The Journal of Endocrinology 113 (3): R7–9. doi:10.1677/joe.0.113R007. PMID 3625091. 
  80. ^ Soloway MS, Schellhammer PF, Smith JA, Chodak GW, Vogelzang NJ, Kennealey GT (Dec 1995). "Bicalutamide in the treatment of advanced prostatic carcinoma: a phase II noncomparative multicenter trial evaluating safety, efficacy and long-term endocrine effects of monotherapy". The Journal of Urology 154 (6): 2110–4. doi:10.1016/S0022-5347(01)66709-0. PMID 7500470. 
  81. ^ a b Gao W, Dalton JT (Mar 2007). "Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)". Drug Discovery Today 12 (5-6): 241–8. doi:10.1016/j.drudis.2007.01.003. PMC 2072879. PMID 17331889. 
  82. ^ a b Eri LM, Haug E, Tveter KJ (Mar 1995). "Effects on the endocrine system of long-term treatment with the non-steroidal anti-androgen Casodex in patients with benign prostatic hyperplasia". British Journal of Urology 75 (3): 335–40. doi:10.1111/j.1464-410X.1995.tb07345.x. PMID 7537602. 
  83. ^ Sieber PR (Dec 2007). "Treatment of bicalutamide-induced breast events". Expert Review of Anticancer Therapy 7 (12): 1773–9. doi:10.1586/14737140.7.12.1773. PMID 18062751. 
  84. ^ Kasperk CH, Wergedal JE, Farley JR, Linkhart TA, Turner RT, Baylink DJ (Mar 1989). "Androgens directly stimulate proliferation of bone cells in vitro". Endocrinology 124 (3): 1576–8. doi:10.1210/endo-124-3-1576. PMID 2521824. 
  85. ^ Manolagas SC, Jilka RL, Girasole G, Passeri G, Bellido T (1993). "Estrogen, cytokines, and the control of osteoclast formation and bone resorption in vitro and in vivo". Osteoporosis International. 3 Suppl 1: 114–6. doi:10.1007/BF01621882. PMID 8461536. 
  86. ^ Vanderschueren D, Gaytant J, Boonen S, Venken K (Jun 2008). "Androgens and bone". Current Opinion in Endocrinology, Diabetes, and Obesity 15 (3): 250–4. doi:10.1097/MED.0b013e3282fe6ca9. PMID 18438173. 
  87. ^ a b c Wibowo E, Schellhammer P, Wassersug RJ (Jan 2011). "Role of estrogen in normal male function: clinical implications for patients with prostate cancer on androgen deprivation therapy". The Journal of Urology 185 (1): 17–23. doi:10.1016/j.juro.2010.08.094. PMID 21074215. 
  88. ^ a b c Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S (Jul 2011). "Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal". BJU International 108 (1): 110–5. doi:10.1111/j.1464-410X.2010.09764.x. PMID 20955264. 
  89. ^ McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP (Feb 2006). "Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer". BJU International 97 (2): 247–54. doi:10.1111/j.1464-410X.2005.06051.x. PMID 16430622. 
  90. ^ Iversen P, Johansson JE, Lodding P, Lukkarinen O, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Carroll K (Nov 2004). "Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6". The Journal of Urology 172 (5 Pt 1): 1871–6. doi:10.1097/01.ju.0000139719.99825.54. PMID 15540741. 
  91. ^ a b Wibowo E, Wassersug RJ (Sep 2013). "The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy". Critical Reviews in Oncology/Hematology 87 (3): 224–38. doi:10.1016/j.critrevonc.2013.01.006. PMID 23484454. 
  92. ^ a b King, S. R. (2008). "Emerging Roles for Neurosteroids in Sexual Behavior and Function". Journal of Andrology 29 (5): 524–533. doi:10.2164/jandrol.108.005660. ISSN 0196-3635. PMID 18567641. 
  93. ^ a b Morali G, Oropeza MV, Lemus AE, Perez-Palacios G (1994). "Mechanisms regulating male sexual behavior in the rat: role of 3 alpha- and 3 beta-androstanediols". Biol. Reprod. 51 (3): 562–71. doi:10.1095/biolreprod51.3.562. PMID 7803627. 
  94. ^ Sánchez Montoya EL, Hernández L, Barreto-Estrada JL, Ortiz JG, Jorge JC (2010). "The testosterone metabolite 3α-diol enhances female rat sexual motivation when infused in the nucleus accumbens shell". J Sex Med 7 (11): 3598–609. doi:10.1111/j.1743-6109.2010.01937.x. PMC 4360968. PMID 20646182. 
  95. ^ Frye CA, Edinger KL, Lephart ED, Walf AA (2010). "3alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats". Front Aging Neurosci 2: 15. doi:10.3389/fnagi.2010.00015. PMC 2874398. PMID 20552051. 
  96. ^ Huang, Q; Zhu, H; Fischer, D; Zhou, J (2008). "An estrogenic effect of 5α-androstane-3β, 17β-diol on the behavioral response to stress and on CRH regulation". Neuropharmacology 54 (8): 1233–1238. doi:10.1016/j.neuropharm.2008.03.016. ISSN 0028-3908. 
  97. ^ Frye, C; Koonce, C; Edinger, K; Osborne, D; Walf, A (2008). "Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice". Hormones and Behavior 54 (5): 726–734. doi:10.1016/j.yhbeh.2008.07.013. ISSN 0018-506X. 
  98. ^ Wolf-Bernhard Schill; Frank H. Comhaire; Timothy B. Hargreave (26 August 2006). Andrology for the Clinician. Springer Science & Business Media. pp. 76–. ISBN 978-3-540-33713-3. 
  99. ^ John P. Mulhall (21 February 2013). Fertility Preservation in Male Cancer Patients. Cambridge University Press. pp. 84–. ISBN 978-1-139-61952-3. 
  100. ^ a b Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1372–1373. ISBN 978-1-60913-345-0. 
  101. ^ a b c Bambury RM, Scher HI (2015). "Enzalutamide: Development from bench to bedside". Urol. Oncol. 33 (6): 280–8. doi:10.1016/j.urolonc.2014.12.017. PMID 25797385. 
  102. ^ a b Pinto Á (2014). "Beyond abiraterone: new hormonal therapies for metastatic castration-resistant prostate cancer". Cancer Biol. Ther. 15 (2): 149–55. doi:10.4161/cbt.26724. PMC 3928129. PMID 24100689. 
  103. ^ a b Zhu Y, Liu C, Armstrong C, Lou W, Sandher A, Gao AC (May 2015). "Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer". Clinical Cancer Research. doi:10.1158/1078-0432.CCR-15-0269. PMID 25995342. 
  104. ^ a b Fenner A (Jul 2015). "Prostate cancer: Antiandrogens reverse docetaxel resistance via ABCB1 inhibition". Nature Reviews. Urology 12 (7): 361. doi:10.1038/nrurol.2015.135. PMID 26057062. 
  105. ^ a b Armstrong CM, Gao AC (2015). "Drug resistance in castration resistant prostate cancer: resistance mechanisms and emerging treatment strategies". Am J Clin Exp Urol 3 (2): 64–76. PMC 4539108. PMID 26309896. 
  106. ^ a b c Mast N, Lin JB, Pikuleva IA (2015). "Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy". Mol. Pharmacol. 88 (3): 428–36. doi:10.1124/mol.115.099598. PMID 26082378. 
  107. ^ a b c d e Tyrrell CJ, Iversen P, Tammela T, Anderson J, Björk T, Kaisary AV, Morris T (Sep 2006). "Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration". BJU International 98 (3): 563–72. doi:10.1111/j.1464-410X.2006.06275.x. PMID 16771791. 
  108. ^ Lunglmayr G (1989). "Casodex (ICI 176,334), a new, non-steroidal anti-androgen. Early clinical results". Horm. Res. 32 Suppl 1: 77–81. doi:10.1159/000181316. PMID 2515147. 
  109. ^ Translational Breast Cancer Research Consortium (TBCRC) (2012). "Targeting the androgen receptor (AR) in women with AR+ ER-/PR- metastatic breast cancer (MBC)". J Clin Oncol (suppl): abstract 1006). 
  110. ^ Clinical trial number NCT00468715 for "Bicalutamide in Treating Patients With Metastatic Breast Cancer" at
  111. ^ Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA (Oct 2013). "Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer". Clinical Cancer Research 19 (19): 5505–12. doi:10.1158/1078-0432.CCR-12-3327. PMC 4086643. PMID 23965901. 
  112. ^ Levine D, Park K, Juretzka M, Esch J, Hensley M, Aghajanian C, Lewin S, Konner J, Derosa F, Spriggs D, Iasonos A, Sabbatini P (Dec 2007). "A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission". Cancer 110 (11): 2448–56. doi:10.1002/cncr.23072. PMID 17918264. 

External links[edit]