Darolutamide (ODM-201) for the treatment of prostate cancer

@article{Shore2017DarolutamideF,
  title={Darolutamide (ODM-201) for the treatment of prostate cancer},
  author={Neal D. Shore},
  journal={Expert Opinion on Pharmacotherapy},
  year={2017},
  volume={18},
  pages={945 - 952}
}
  • N. Shore
  • Published 24 May 2017
  • Medicine, Biology
  • Expert Opinion on Pharmacotherapy
ABSTRACT Introduction: Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide… 
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Non-metastatic castration-resistant prostate cancer: current status and future directions
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References

SHOWING 1-10 OF 40 REFERENCES
ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer
TLDR
ODM-201, a new-generation AR inhibitor with a unique molecular structure, is reviewed, in the treatment of CRPC, at a disease stage for which there is currently no approved treatment.
Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: results from the STAMPEDE and CHAARTED trials
TLDR
Results of the STAMPEDE trial in men with high-risk locally advanced or metastatic prostate cancer initiating long-term hormone therapy show that docetaxel in addition to ADT should be considered SOC for men with newly diagnosed mHSPC.
Enzalutamide in metastatic prostate cancer before chemotherapy.
TLDR
Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer.
Abiraterone and increased survival in metastatic prostate cancer.
TLDR
The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy.
Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer
TLDR
It is concluded that the success of PCa therapies in the future depends on targeting molecular mechanisms underlying tumor recurrence that still may affect AR at pre-receptor, receptor, and post-rereceptor levels.
ARAMIS trial: Efficacy and safety of ODM-201 in men with high-risk nonmetastatic castration-resistant prostate cancer.
TLDR
The ARAMIS trial will evaluate the efficacy and safety of ODM-201 in high-risk nmCRPC pts, a novel second-generation oral androgen receptor inhibitor that has demonstrated a tolerable safety profile and antineoplastic activity in progressive CRPC.
AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
BACKGROUND The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a
Androgen receptor targeting drugs in castration‐resistant prostate cancer and mechanisms of resistance
TLDR
Promising therapies and novel biomarkers, such as AR‐V7, may lead to improved outcomes for CRPC patients and several novel agents may overcome resistance mechanisms.
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