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Journal of Cosmetic Dermatology Oct 2022Female pattern hair loss (FPHL) is the most common form of alopecia in women. FPHL may compromise body image and strongly affect self-esteem, negatively impacting... (Review)
Review
Female pattern hair loss (FPHL) is the most common form of alopecia in women. FPHL may compromise body image and strongly affect self-esteem, negatively impacting quality of life. Currently, the only Food and Drug Administration (FDA) approved drug for its treatment is topical minoxidil, with a variable response rate. Recently, a few studies in FPHL have pointed out bicalutamide as an emergent selective androgen receptor antagonist with a favorable safety and tolerability profile. This review aimed to summarize and discuss the key information on this new therapy for FPHL. Bicalutamide has no diuretic effect. It does not cross the blood-brain barrier, and it has little effect on serum luteinizing hormone. Additionally, bicalutamide was found to be effective on women presenting with other features of hyperandrogenism such as seborrhea, acne, and hirsutism with mild and well-tolerated adverse effects. Despite the high prevalence and psychosocial impairment, FPHL treatment remains challenging. Therefore, although future prospective, comparative, randomized clinical trials are essential to establish the ideal dose and efficacy of the drug, oral bicalutamide appears to be a promising option to expand the arsenal of FPHL treatment.
Topics: Female; Humans; Quality of Life; Dermatologists; Alopecia; Minoxidil
PubMed: 35032336
DOI: 10.1111/jocd.14773 -
The Lancet. Oncology Oct 2022Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant... (Randomized Controlled Trial)
Randomized Controlled Trial
Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial.
BACKGROUND
Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer.
METHODS
CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478.
FINDINGS
Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group.
INTERPRETATION
In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile.
FUNDING
Jiangsu Hengrui Pharmaceuticals.
Topics: Androgen Antagonists; Androgens; Anilides; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds
PubMed: 36075260
DOI: 10.1016/S1470-2045(22)00507-1 -
International Journal of Radiation... Jun 2022
Topics: Androgen Antagonists; Anilides; Humans; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds
PubMed: 35569476
DOI: 10.1016/j.ijrobp.2022.01.037 -
Clinical Pharmacokinetics 2004Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once daily as monotherapy for the treatment of early (localised or locally advanced)... (Review)
Review
Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once daily as monotherapy for the treatment of early (localised or locally advanced) nonmetastatic prostate cancer. It is used at a dosage of 50 mg once daily in combination with a luteinising hormone-releasing hormone analogue or surgical castration for the treatment of advanced prostate cancer. Bicalutamide is a racemate and its antiandrogenic activity resides almost exclusively in the (R)-enantiomer, with little, if any, activity in the (S)-enantiomer. (R)-Bicalutamide is slowly and saturably absorbed, but absorption is unaffected by food. It has a long plasma elimination half-life (1 week) and accumulates about 10-fold in plasma during daily administration. (S)-Bicalutamide is much more rapidly absorbed and cleared from plasma; steady-state concentrations (Css) of (R)-bicalutamide are 100-fold higher than those of (S)-bicalutamide. Css increases linearly with doses up to 50 mg, but nonlinearly at higher doses, reaching a plateau above 300 mg. Css is higher in Japanese than in Caucasians, but no relationship with degree of renal impairment, bodyweight or age exists. Although mild-to-moderate hepatic impairment does not affect pharmacokinetics, there is evidence for slower elimination of (R)-bicalutamide in subjects with severe hepatic impairment. Bicalutamide metabolites are excreted almost equally in urine and faeces with little or no unchanged drug excreted in urine; conversely, unchanged drug predominates in plasma. Bicalutamide in faeces is thought to arise from hydrolysis of bicalutamide glucuronide and from unabsorbed drug. Bicalutamide appears to be cleared almost exclusively by metabolism; this is largely mediated by cytochrome P450 (CYP) for (R)-bicalutamide, but glucuronidation is the predominant metabolic route for (S)-bicalutamide. (S)-Bicalutamide is metabolised in vitro by CYP3A4, and it is probable that this isoenzyme is also responsible for the metabolism of (R)-bicalutamide. In vitro data suggest that (R)-bicalutamide has the potential to inhibit CYP3A4 and, to a lesser extent, CYP2C9, 2C19 and 2D6. However, using midazolam as a specific CYP3A4 marker, no clinically relevant inhibition is observed in vivo with bicalutamide 150mg. Although bicalutamide is a CYP inducer in laboratory animals, dosages < or = 150 mg/day have shown no evidence of enzyme induction in humans. Daily administration of bicalutamide increases circulating levels of gonadotrophins and sex hormones; although testosterone increases by up to 80%, concentrations in most patients remain within the normal range. Bicalutamide produces a dose-related decrease in prostate-specific antigen (PSA) at dosages < or = 150 mg/day. However, little relationship is observed between median PSA reduction and (R)-bicalutamide Css.
Topics: Administration, Oral; Androgen Antagonists; Anilides; Biological Availability; Blood Proteins; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Humans; Male; Nitriles; Prostatic Neoplasms; Protein Binding; Time Factors; Tosyl Compounds
PubMed: 15509184
DOI: 10.2165/00003088-200443130-00003 -
Drugs 2002Bicalutamide is an oral, once-daily nonsteroidal antiandrogen. Its efficacy in localised or locally advanced prostate cancer is currently being investigated as part of... (Review)
Review
Bicalutamide is an oral, once-daily nonsteroidal antiandrogen. Its efficacy in localised or locally advanced prostate cancer is currently being investigated as part of the Early Prostate Cancer (EPC) programme. In the EPC programme, bicalutamide 150 mg/day, as an adjunct to radiotherapy, radical prostatectomy or watchful waiting, significantly reduced the risk of objective disease progression, the incidence of bone metastases and the risk of prostate specific antigen progression compared with placebo (p < 0.0001 for all three parameters) after a median follow-up of 3 years. Survival data are currently immature, with an overall mortality rate of 6% in both treatment arms. On two nonblind, randomised trials, bicalutamide 150 mg/day monotherapy was as effective as medical or surgical castration in terms of overall survival in patients with locally advanced nonmetastatic prostate cancer. After a median follow-up of 6.3 years, median survival was 63.5 and 69.9 months for bicalutamide and castration, respectively; time to disease progression was also similar between treatment groups. Bicalutamide recipients reported a significantly smaller loss in sexual interest and a better physical capacity than recipients of castration (p
Bicalutamide is well tolerated in studies of up to 6.3 years' duration. Topics: Administration, Oral; Androgen Antagonists; Anilides; Chemotherapy, Adjuvant; Humans; Male; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Tosyl Compounds; Treatment Outcome
PubMed: 12421104
DOI: 10.2165/00003495-200262170-00006 -
The Prostate Jan 1998Bicalutamide (Casodex) is a new nonsteroidal antiandrogen developed for use in patients with prostate cancer. The efficacy and tolerability of bicalutamide as... (Review)
Review
BACKGROUND
Bicalutamide (Casodex) is a new nonsteroidal antiandrogen developed for use in patients with prostate cancer. The efficacy and tolerability of bicalutamide as monotherapy and as combination therapy for patients with advanced prostate cancer have been evaluated in randomized clinical trials. Clinical trials are currently in progress to further evaluate bicalutamide as monotherapy in patients with advanced stages of disease and as adjuvant or first-line therapy in patients with early-stage disease.
METHODS
A review of published trials of bicalutamide focusing on dose-ranging investigations, phase II and phase III monotherapy trials, a phase III trial of combined androgen blockade, and a safety overview.
RESULTS
In dose-ranging trials, bicalutamide doses of 10-200 elicited biochemical, objective, and subjective responses; higher bicalutamide doses (up to 600 mg) have also been evaluated. A 50-mg daily dose of bicalutamide was initially evaluated as monotherapy in phase II and phase III trials; in subsequent trials, a 150-mg daily dose was investigated. A 150-mg daily dose is considered to provide equivalent survival outcome compared with castration in patients with locally advanced prostate cancer, whereas the benefits of a better quality of life and better palliation with the 150-mg daily bicalutamide dose relative to castration in patients with metastatic disease needs to be balanced against the small shortfall (median difference, 42 days) in survival. In combination with a luteinizing hormone-releasing hormone agonist analogue (LHRH-A), a 50-mg daily dose of bicalutamide has equivalent efficacy to a corresponding flutamide (250 mg three times daily) combination regimen. Treatment with the bicalutamide combination regimen resulted in a longer median survival than with the flutamide combination regimen. Bicalutamide is well tolerated when used as monotherapy or in combination with a LHRH-A. The benefits of bicalutamide as monotherapy include retention of libido and sexual potency and as combination therapy a lower incidence of diarrhea relative to flutamide.
CONCLUSIONS
A 50-mg daily dose of bicalutamide is sufficient when given in combination with an agent, such as a LHRH-A, that lowers serum testosterone, but higher doses of bicalutamide may be needed when the drug is given as monotherapy. Bicalutamide, 50-mg daily, is a logical first choice for antiandrogen therapy when used in combination with an LHRH-A for the treatment of patients with advanced prostate cancer. Bicalutamide 150-mg daily is considered an effective monotherapy for use in patients with locally advanced disease. Additional clinical trials are currently in progress to further evaluate bicalutamide as a monotherapy for advanced prostate cancer and to assess its value as adjuvant or first-line therapy for early-stage prostate cancer.
Topics: Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds
PubMed: 9428389
DOI: 10.1002/(sici)1097-0045(19980101)34:1<61::aid-pros8>3.0.co;2-n -
Drugs & Aging May 1998Bicalutamide is a nonsteroidal antiandrogen with a long elimination half-life (t1/2) that permits once-daily administration. When combined with a gonadorelin... (Review)
Review
UNLABELLED
Bicalutamide is a nonsteroidal antiandrogen with a long elimination half-life (t1/2) that permits once-daily administration. When combined with a gonadorelin (gonadotrophin releasing hormone; GnRH) agonist in maximum androgen blockade (MAB) regimens, bicalutamide 50 mg once daily is at least as effective as flutamide 250 mg 3 times daily, as shown in a large randomised trial. Rate of treatment failure, the primary end-point, was significantly lower at 49 weeks with bicalutamide in this study, mainly because of a lower rate of withdrawal due to adverse events. Final results at a median follow-up of 160 weeks revealed longer median times to progression and death with bicalutamide than flutamide, but between-group differences were not significant overall. Although early trials demonstrated clinical benefits with bicalutamide 50 mg/day as monotherapy, the drug in this dosage is less effective than castration. Increasing the dosage to 150 mg/day has improved its efficacy in patients with non-metastatic disease: combined data from 2 trials demonstrate similar survival with bicalutamide in this dosage compared with castration. Accumulating evidence from these and other studies indicates that sexual interest appears to be better preserved with bicalutamide than with castration. The tolerability profile of bicalutamide is characteristic of antiandrogens, with breast pain and gynaecomastia occurring most often. Bicalutamide has not been causally associated with problems such as interstitial pneumonitis and difficulty with light/dark adaptation seen with nilutamide, and in a 50 mg/day dosage causes a lower incidence of diarrhoea than flutamide 750 mg/day. Changes in hepatic function are generally transient and resolve or improve during therapy or after bicalutamide treatment is withdrawn.
CONCLUSIONS
Bicalutamide, with its once-daily regimen and good tolerability, is an attractive option when combined with a GnRH agonist in patients with advanced prostate cancer who are suitable to receive MAB regimens. The role of bicalutamide as monotherapy in the management of this common malignancy is currently being assessed.
Topics: Androgen Antagonists; Anilides; Animals; Antineoplastic Agents; Humans; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds
PubMed: 9606617
DOI: 10.2165/00002512-199812050-00006 -
The Journal of Urology Dec 2003The current evidence is considered to support 150 mg of the nonsteroidal antiandrogen bicalutamide for early stage prostate cancer. (Clinical Trial)
Clinical Trial Randomized Controlled Trial Review
PURPOSE
The current evidence is considered to support 150 mg of the nonsteroidal antiandrogen bicalutamide for early stage prostate cancer.
MATERIALS AND METHODS
Data from phase III trials of 150 mg bicalutamide monotherapy for locally advanced disease are discussed. In addition, the first overall results are examined from the bicalutamide early prostate cancer program conducted at a median followup of 3 years, in which patients with localized or locally advanced disease were randomized to receive 150 mg bicalutamide or placebo as well as standard care.
RESULTS
Mature data from phase III studies have shown that 150 mg bicalutamide monotherapy provide similar survival outcome to that observed with castration in patients with locally advanced (M0) disease. Moreover, 150 mg bicalutamide have benefits over castration in terms of quality of life, particularly sexual interest and physical capacity, and preservation of bone mineral density. In the bicalutamide early prostate cancer program 150 mg significantly reduced the risk of objective progression in patients with localized or locally advanced disease at 3 years of median followup, with the greatest benefit seen in patients with poorer prognosis. Followup is ongoing to further determine the benefit of 150 mg bicalutamide in early prostate cancer.
CONCLUSIONS
Bicalutamide is emerging as a useful treatment option for early prostate cancer.
Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Clinical Trials, Phase III as Topic; Disease Progression; Humans; Male; Nitriles; Prognosis; Prostatic Neoplasms; Quality of Life; Sexual Behavior; Tosyl Compounds
PubMed: 14610410
DOI: 10.1097/01.ju.0000096491.61731.38 -
Neurotherapeutics : the Journal of the... Mar 2023Spinal and bulbar muscular atrophy (SBMA) is characterized by motor neuron (MN) degeneration that leads to slowly progressive muscle weakness. It is considered a...
Spinal and bulbar muscular atrophy (SBMA) is characterized by motor neuron (MN) degeneration that leads to slowly progressive muscle weakness. It is considered a neuromuscular disease since muscle has a primary role in disease onset and progression. SBMA is caused by a CAG triplet repeat expansion in the androgen receptor (AR) gene. The translated poly-glutamine (polyQ) tract confers a toxic gain of function to the mutant AR altering its folding, causing its aggregation into intracellular inclusions, and impairing the autophagic flux. In an in vitro SBMA neuronal model, we previously showed that the antiandrogen bicalutamide and trehalose, a natural disaccharide stimulating autophagy, block ARpolyQ activation, reduce its nuclear translocation and toxicity and facilitate the autophagic degradation of cytoplasmic AR aggregates. Here, in a knock-in SBMA mouse model (KI AR113Q), we show that bicalutamide and trehalose ameliorated SBMA pathology. Bicalutamide reversed the formation of the AR insoluble forms in KI AR113Q muscle, preventing autophagic flux blockage. We demonstrated that apoptosis is activated in KI AR113Q muscle, and that both compounds prevented its activation. We detected a decrease of mtDNA and an increase of OXPHOS enzymes, already at early symptomatic stages; these alterations were reverted by trehalose. Overall, bicalutamide and/or trehalose led to a partial recovery of muscle morphology and function, and improved SBMA mouse motor behavior, inducing an extension of their survival. Thus, bicalutamide and trehalose, by counteracting ARpolyQ toxicity in skeletal muscle, are valuable candidates for future clinical trials in SBMA patients.
Topics: Mice; Animals; Bulbo-Spinal Atrophy, X-Linked; Trehalose; Receptors, Androgen; Muscular Atrophy, Spinal; Anilides; Mice, Transgenic
PubMed: 36717478
DOI: 10.1007/s13311-023-01343-x -
Drugs 2006Bicalutamide (Casodex) is a competitive androgen receptor antagonist that inactivates androgen-regulated prostate cell growth and function, leading to cell apoptosis and... (Review)
Review
Bicalutamide (Casodex) is a competitive androgen receptor antagonist that inactivates androgen-regulated prostate cell growth and function, leading to cell apoptosis and inhibition of prostate cancer growth. It is administered orally as a once-daily dose. In the EU and a number of other countries, bicalutamide 150 mg/day is approved in men with locally advanced nonmetastatic prostate cancer as immediate therapy either as an adjuvant to active treatment or as monotherapy as an alternative to surgical or medical castration. Combined analysis of the three trials that comprise the bicalutamide Early Prostate Cancer (EPC) programme showed that bicalutamide administered in conjunction with standard care in men with locally advanced prostate cancer offers disease-free survival benefits over standard care alone and is generally well tolerated. Overall survival was improved to a greater extent in the subgroup of patients who received bicalutamide plus radiation therapy compared with radiation therapy alone. Men with localised prostate cancer do not benefit from the addition of bicalutamide to standard care. Combined analysis of two other studies in men with locally advanced prostate cancer show that bicalutamide monotherapy offers better tolerability and higher health-related quality-of-life (HR-QOL) scores for sexual interest and physical capacity compared with surgical or medical castration, while achieving disease-free and overall survival durations that were not significantly different. Thus, when treatment options are being evaluated, bicalutamide as adjuvant therapy or monotherapy should be considered as an alternative to other available hormonal therapies in men with locally advanced prostate cancer, especially in those who wish to maintain an active lifestyle.
Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Chemotherapy, Adjuvant; Clinical Trials as Topic; Humans; Male; Middle Aged; Nitriles; Orchiectomy; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome
PubMed: 16706554
DOI: 10.2165/00003495-200666060-00007