Effects of nilutamide: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Major Research Findings

Nilutamide is a nonsteroidal antiandrogen that has been shown to be effective in treating prostate cancer. 1 、 11 、、 8 、 It works by blocking the effects of androgens, which are hormones that promote the growth of prostate cancer cells. 17 、 19 Nilutamide can be used as a single therapy or in combination with other treatments. 11 、 8 It has been shown to reduce bone pain and improve performance status. 1 Nilutamide has been shown to inhibit the production of prostate-specific antigen (PSA), which is a protein that is often elevated in men with prostate cancer. 12 It has been shown to increase nitric oxide production in vascular endothelial cells by activating endothelial nitric oxide synthase (eNOS). 2 Nilutamide is metabolized in various tissues in rats, including the lung, liver, brain, kidney, heart, blood, and intestines. 10 It can also be metabolized by bacteria in the intestinal lumen. 10 Nilutamide has been reported to cause pneumotoxicity and hepatotoxicity in humans. 10 It has been shown to induce mitochondrial permeability transition. 15 In human prostate cancer cells, nilutamide can activate the androgen receptor (AR). 7 Nilutamide has been shown to have lower tolerability compared to flutamide or bicalutamide. 8 It can cause side effects such as interstitial pneumonitis, delayed adaptation to darkness, and alcohol intolerance. 8 It can also affect liver function. 11 Nilutamide has been shown to cause a lower incidence of diarrhea compared to flutamide. 11 It has been shown to preserve sexual desire better than castration. 11 Nilutamide binds to AR with lower affinity compared to flutamide or bicalutamide. 17 In conditions of AR gene amplification or mutations, nilutamide can exhibit agonist activity and fail to inhibit AR, leading to relapse into castration-resistant prostate cancer (CRPC). 17 Nilutamide has been shown to be more potent than bicalutamide or flutamide. 17 It can be used in the development of new drugs that inhibit AR by binding to colchicine. 18 It can interact with pesticides such as cypermethrin. 16 Nilutamide may be associated with an increased incidence of interstitial lung disease (ILD) in men with prostate cancer who are receiving hormone therapy. 5 It has been shown to be active against juvenile and adult Schistosoma mansoni in mice. 9 Nilutamide has been shown to have different in vitro effects on androgen-sensitive parameters compared to other pure antiandrogens such as OH-flutamide, Casodex, and nilutamide. 3 It can lead to antiandrogen withdrawal syndrome, which is a temporary improvement in a subpopulation of prostate cancer patients following cessation of an antiandrogen. 7 Nilutamide is often used as part of standard androgen deprivation therapy, which includes androgen deprivation via castration. 14 Castration in combination with nilutamide has been shown to be more effective than androgen deprivation therapy alone. 14

Benefits and Risks

Benefits Summary

Nilutamide is an effective treatment for prostate cancer and can reduce bone pain and improve performance status. 1 It has been shown to inhibit the production of prostate-specific antigen (PSA). 12 It has been shown to increase nitric oxide production in vascular endothelial cells by activating endothelial nitric oxide synthase (eNOS). 2 It may preserve sexual desire better than other antiandrogens. 11 It has been shown to be more potent than bicalutamide or flutamide. 17 It can be used in the development of new drugs that inhibit AR by binding to colchicine. 18

Risks Summary

Nilutamide can cause side effects. 1 、 11 、 8 、 10 、 15 、、 14 It can cause side effects such as interstitial pneumonitis, delayed adaptation to darkness, and alcohol intolerance. 8 It can also affect liver function. 11 It has been shown to have lower tolerability compared to flutamide or bicalutamide. 8 In conditions of AR gene amplification or mutations, nilutamide can exhibit agonist activity and fail to inhibit AR, leading to relapse into castration-resistant prostate cancer (CRPC). 17 It can interact with pesticides such as cypermethrin. 16 Nilutamide may be associated with an increased incidence of interstitial lung disease (ILD) in men with prostate cancer who are receiving hormone therapy. 5 It is important to discuss the use of nilutamide with your doctor.

Research Comparisons

Research Similarities

Multiple studies have shown that nilutamide is effective in treating prostate cancer. 1 、 11 、 4 It has been shown to reduce bone pain and improve performance status. 1 It works by blocking the effects of androgens, which are hormones that promote the growth of prostate cancer cells. 17 、 19

Research Differences

The incidence of side effects of nilutamide varies across studies. 8 Nilutamide binds to AR with lower affinity compared to flutamide or bicalutamide. 17 It has been shown to be more potent than bicalutamide or flutamide. 17

Consistency and Contradictions of Results

Research results suggest that nilutamide is an effective treatment for prostate cancer. 1 、 11 、 4 However, it is also clear that nilutamide is a drug with the potential for side effects. 1 、 11 、 8 、 10 、 15 、、 14 The incidence of side effects of nilutamide varies across studies. 8

Real-World Application Notes

Nilutamide is an effective treatment for prostate cancer, but it has the potential for side effects. 1 、 11 、 8 、 10 、 15 、、 14 It is crucial to discuss the use of nilutamide with your doctor. Nilutamide is an effective treatment for prostate cancer, but it has the potential for side effects. 1 、 11 、 8 、 10 、 15 、、 14 It is crucial to discuss the use of nilutamide with your doctor.

Limitations of Current Research

There is not enough research on the side effects of nilutamide. 8 In conditions of AR gene amplification or mutations, nilutamide can exhibit agonist activity and fail to inhibit AR, leading to relapse into castration-resistant prostate cancer (CRPC). 17 More research is needed on the side effects of nilutamide.

Future Research Directions

More research is needed to investigate the side effects of nilutamide in greater detail. 8 More studies are also needed to compare the effectiveness of nilutamide with other antiandrogens. 11 In conditions of AR gene amplification or mutations, nilutamide can exhibit agonist activity and fail to inhibit AR, leading to relapse into castration-resistant prostate cancer (CRPC). 17 Nilutamide can be used in the development of new drugs that inhibit AR by binding to colchicine. 18 More research is needed to better understand the safety of nilutamide.

Conclusion

Nilutamide is an effective treatment for prostate cancer, but it also has the potential for side effects. 1 、 11 、 8 、 10 、 15 、、 14 It is crucial to discuss the use of nilutamide with your doctor. Nilutamide is an effective treatment for prostate cancer, but it also has the potential for side effects. 1 、 11 、 8 、 10 、 15 、、 14 It is crucial to discuss the use of nilutamide with your doctor.

Literature analysis of 19 papers
Positive Content
14
Neutral Content
1
Negative Content
4
Article Type
1
1
1
6
19
1.

Castration plus nilutamide vs castration plus placebo in advanced prostate cancer. A review.

Author: Du PlessisD J

Improve performance status
Increase regression
Reduce bone pain
Alcohol intolerance
Gastrointestinal disorders
Visual disorders

Nilutamide improves the efficacy of castration in patients with prostatic cancer.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

2.

Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/akt pathway.

Author: YuJing, AkishitaMasahiro, EtoMasato, OgawaSumito, SonBo-Kyung, KatoShigeaki, OuchiYasuyoshi, OkabeTetsuro

Increased NO production
Vasodilatation

This study investigated the effect of testosterone on nitric oxide (NO) synthesis and its molecular mechanism in human aortic endothelial cells (HAEC). Testosterone rapidly induced NO production through AR-dependent activation of eNOS. This activation involved PI3-kinase/Akt signaling and direct interaction of AR with p85alpha.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Comparison of in vitro effects of the pure antiandrogens OH-flutamide, Casodex, and nilutamide on androgen-sensitive parameters.

Author: SimardJ, SinghS M, LabrieF

Prostate cancer treatment

The in vitro antiandrogenic activity of OH-flutamide, Casodex, and nilutamide was compared.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Efficacy and Safety of Nilutamide in Patients with Metastatic Prostate Cancer who Underwent Orchiectomy: A Systematic Review and Metaanalysis.

Author: RashidMuhammed, ShamshavaliK, ChhabraManik

Treats metastatic prostate cancer

This study evaluated the efficacy and safety of nilutamide in metastatic prostate cancer patients who underwent orchiectomy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

5.

Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System.

Author: WuBin, ShenPengfei, YinXi, YuLei, WuFengbo, ChenChen, LiJian, XuTing

ILD events

This pharmacovigilance analysis investigated interstitial lung disease (ILD) in men with prostate cancer receiving hormone therapy using the FDA Adverse Event Reporting System (FAERS) database. ILD events were significantly associated with nilutamide, flutamide, bicalutamide, goserelin, degarelix, and apalutamide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer.

Author: MahlerC, VerhelstJ, DenisL

Preserves sexual function
Prostate cancer treatment
Gynecomastia

Antiandrogens, such as bicalutamide, are used to treat prostate cancer, particularly in metastatic cases. Bicalutamide has a longer half-life than flutamide, allowing once-daily administration, and is associated with fewer adverse effects compared to nilutamide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Androgen receptor gene mutations in prostate cancer. Implications for disease progression and therapy.

Author: CuligZ, HobischA, HittmairA, CronauerM V, RadmayrC, BartschG, KlockerH

Prostate cancer treatment
Antiandrogen withdrawal syndrome

Androgen receptor mutations have been found in human prostatic tumours. These mutations may explain, at least in part, the antiandrogen withdrawal syndrome. Further studies on androgen receptor alterations in prostate cancer should focus on metastatic specimens obtained from the late stages of this disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Activity of antiandrogens against juvenile and adult Schistosoma mansoni in mice.

Author: KeiserJennifer, VargasMireille, VennerstromJonathan L

Schistosomiasis treatment

The antiandrogen nilutamide showed promising antischistosomal properties in both in vivo and in vitro studies. In mice infected with Schistosoma mansoni, nilutamide reduced total worm burden by 85% and female worm burden by 71%. A combination of nilutamide and praziquantel also demonstrated significant worm burden reductions. In vitro, cyproterone acetate killed schistosomes within 15 hours, while bicalutamide, nilutamide, and flutamide reduced the movement of adult worms.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Distribution of nitroreductive activity toward nilutamide in rat.

Author: AskKjetil, DécologneNathalie, AsareNana, HolmeJørn A, ArturYves, PelczarHélène, CamusPhilippe

Hepatotoxicity
Pneumotoxicity

Nilutamide, an antiandrogen used to treat prostate carcinoma, is metabolized by nitroreductases in various tissues, potentially contributing to its pneumotoxicity and hepatotoxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Bicalutamide in advanced prostate cancer. A review.

Author: GoaK L, SpencerC M

Preserves sexual interest
Prostate cancer treatment
Well-tolerated
Breast pain
Gynecomastia
Hepatic issues

Bicalutamide, a nonsteroidal antiandrogen, offers a once-daily administration schedule and is well-tolerated with fewer side effects than flutamide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

Flavonoids can block PSA production by breast and prostate cancer cell lines.

Author: Rosenberg ZandRachel S, JenkinsDavid J A, BrownTheodore J, DiamandisEleftherios P

Prostate cancer treatment

This article explores the use of phytoestrogens as potential androgen-blocking agents in the treatment of prostate cancer, examining their potential for inhibiting androgen-regulated proteins.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

[Hormonal treatment in prostate cancer].

Author: BastideC, BruyèreF, KarsentyG, GuyL, RozetF

Improved prostate cancer treatment

Hormonal treatment is a mainstay in the treatment of locally advanced and metastatic prostate cancer. New therapeutic classes, such as inhibitors of the synthesis of the androgen and new antiandrogens, are now available. These treatments allow for the management of hormone resistance and define the concept of castration-resistant prostate cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : French

14.

Combined androgen blockade for prostate cancer: review of efficacy, safety and cost-effectiveness.

Author: AkazaHideyuki

Prolong overall survival
Treat prostate cancer

Combined androgen blockade (CAB) is a treatment for prostate cancer that involves using an antiandrogen plus castration. This review discusses the feasibility of CAB with bicalutamide for the treatment of prostate cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

16.

Anti-androgen effects of cypermethrin on the amino- and carboxyl-terminal interaction of the androgen receptor.

Author: HuJin-Xia, LiYan-Fang, PanChen, ZhangJin-Peng, WangHong-Mei, LiJing, XuLi-Chun

Anti-androgen

Cypermethrin, a pyrethroid insecticide, was found to exhibit inhibitory effects on the androgen receptor (AR) N/C interaction, a mechanism required for the transcription potential of the AR.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer.

Author: KandilSahar, WestwellAndrew D, McGuiganChristopher

Improved antiproliferative activity
Cross-resistance

This study evaluated the antiproliferative activity of 7-substituted umbelliferone derivatives as potential androgen receptor (AR) antagonists. Compound 7a showed submicromolar inhibitory activity against prostate cancer cells, demonstrating significant improvement over existing clinical antiandrogens.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

A bifunctional colchicinoid that binds to the androgen receptor.

Author: SharifiNima, HamelErnest, LillMarkus A, RisboodPrabhakar, KaneCharles T, HossainMd Tafazzal, JonesAmanda, DaltonJames T, FarrarWilliam L

CRPC treatment

A novel compound that is a conjugate of colchicine and an AR antagonist (cyanonilutamide) was synthesized and evaluated as a potential treatment for castrate-resistant prostate cancer (CRPC). The compound showed binding to both the androgen receptor (AR) and tubulin, and it was more toxic to androgen-independent prostate cancer cells than the combination of colchicine and nilutamide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.

Language : English

19.

Design, synthesis and biological evaluation of novel 5-oxo-2-thioxoimidazolidine derivatives as potent androgen receptor antagonists.

Author: IvachtchenkoAlexandre V, IvanenkovYan A, MitkinOleg D, VorobievAnton A, KuznetsovaIrina V, ShevkunNatalia A, KoryakovaAngela G, KarapetianRuben N, TrifelenkovAndrey S, KravchenkoDmitry V, VeselovMark S, ChufarovaNina V

AR antagonism

(R)-6 (ONC1-13B) and its analogues are potent androgen receptor antagonists with IC50 values in the range of 59-80 nM. These compounds are at least two times more active than bicalutamide, nilutamide, and enzalutamide. They demonstrated good pharmacokinetic profiles in rats.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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