Difference between revisions of "Enzalutamide (Xtandi)"

Revision as of 18:20, 22 March 2024

General information

Class/mechanism: Antiandrogen; androgen receptor inhibitor (ARI) or androgen receptor signaling inhibitor (ARSI). Enzalutamide competitively inhibits testosterone from binding to the androgen receptor, interferes with translocation of the androgen receptor to the nucleus, and inhibits binding to DNA, resulting in decreased prostate cancer proliferation and cell death.^[1]^[2]^[3]
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

Patient drug information

History of changes in FDA indication

2012-08-31: Initial approval for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. (Based on AFFIRM)
2014-09-10: Approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). (No longer needs to be after docetaxel; based on PREVAIL and TERRAIN)
2018-07-13: Approved for patients with castration-resistant prostate cancer (CRPC). (No longer needs to be metatstatic; based on PROSPER_PrCA)
2019-12-16: Approved for patients with metastatic castration-sensitive prostate cancer (mCSPC). (No longer needs to be castration-resistant, if metastatic; based on ARCHES)
2023-11-16: Approved for non-metastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). (No longer needs to be castration-resistant; based on EMBARK)

History of changes in EMA indication

2013-06-21: Initial marketing authorization as Xtandi. Xtandi is indicated for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy. (Based on AFFIRM)
2014-11-28: Extension of indication for the treatment of adult men with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.
2018-10-23: Extension of Indication to include adult men with high-risk non-metastatic castration-resistant prostate cancer (CRPC).
2021-04-30: Extension of Indication to include the treatment of adult men with metastatic hormonesensitive prostate cancer (mHSPC) for Xtandi in combination with androgen deprivation therapy. (Based on ARCHES)

History of changes in Health Canada indication

2013-05-29: Initial notice of compliance

History of changes in PMDA indication

2014-03-24: Initial approval for the treatment of castration-resistant prostate cancer.
2020-05-29: New indication for the treatment of metastatic prostate cancer.

Also known as

Code name: MDV-3100
Brand names: Azel, Bdenza, Bnyx, Capmide, Enzamide, Glenza, Indenza, Xtandi

References

[insert-1] 1.0 ^1.1 Enzalutamide (Xtandi) package insert

[2] Enzalutamide (Xtandi) package insert (locally hosted backup)

[3] Xtandi manufacturer's website

[4] Enzalutamide (Xtandi) patient drug information (Chemocare)

[5] Enzalutamide (Xtandi) patient drug information (UpToDate)

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 ==General information==
-Class/mechanism: Antiandrogen; androgen receptor inhibitor (ARI) or androgen receptor signaling inhibitor (ARSI).  Enzalutamide competitively inhibits testosterone from binding to the androgen receptor, interferes with translocation of the androgen receptor to the nucleus, and inhibits binding to DNA, resulting in decreased prostate cancer proliferation and cell death.<ref name="insert">[http://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf Enzalutamide (Xtandi) package insert]</ref><ref>[[Media:Enzalutamide.pdf | Enzalutamide (Xtandi) package insert (locally hosted backup)]]</ref><ref>[http://xtandi.com/ Xtandi manufacturer's website]</ref>
+Class/mechanism: Antiandrogen; androgen receptor inhibitor (ARI) or androgen receptor signaling inhibitor (ARSI). Enzalutamide competitively inhibits testosterone from binding to the androgen receptor, interferes with translocation of the androgen receptor to the nucleus, and inhibits binding to DNA, resulting in decreased prostate cancer proliferation and cell death.<ref name="insert">[http://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf Enzalutamide (Xtandi) package insert]</ref><ref>[[:File:Enzalutamide.pdf | Enzalutamide (Xtandi) package insert (locally hosted backup)]]</ref><ref>[http://xtandi.com/ Xtandi manufacturer's website]</ref>
 <br>Route: PO
 <br>Extravasation: n/a
-For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer.  Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.
+For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.
 ==Diseases for which it is used==
+*[[Breast cancer, triple negative]]
 *[[Prostate cancer]]
-==Clinical trials==
-*AFFIRM: [http://www.ncbi.nlm.nih.gov/pubmed/22894553 Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (AFFIRM)]<ref>Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller MD, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; the AFFIRM Investigators. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy. N Engl J Med. 2012 Aug 15. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1207506 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22894553 PubMed] [http://clinicaltrials.gov/ct2/show/NCT00974311 ClinicalTrials.gov]</ref>
-*PREVAIL: [http://clinicaltrials.gov/ct2/show/NCT01212991 A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer (PREVAIL)]
 ==Patient drug information==
 *[http://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf Enzalutamide (Xtandi) package insert]<ref name="insert"></ref>
-*[http://chemocare.com/chemotherapy/drug-info/enzalutamide.aspx Enzalutamide (Xtandi) patient drug information (Chemocare)]<ref>[http://chemocare.com/chemotherapy/drug-info/enzalutamide.aspx Enzalutamide (Xtandi) patient drug information (Chemocare)]</ref>
+*[https://chemocare.com/druginfo/enzalutamide.aspx Enzalutamide (Xtandi) patient drug information (Chemocare)]<ref>[https://chemocare.com/druginfo/enzalutamide.aspx Enzalutamide (Xtandi) patient drug information (Chemocare)]</ref>
 *[http://www.uptodate.com/contents/enzalutamide-patient-drug-information Enzalutamide (Xtandi) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/enzalutamide-patient-drug-information Enzalutamide (Xtandi) patient drug information (UpToDate)]</ref>
-==[http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist History of changes in FDA indication]==
+==History of changes in FDA indication==
-*8/31/2012: [http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm317997.htm Initial FDA approval] "for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel."
+*2012-08-31: [http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm317997.htm Initial approval] for the treatment of patients with metastatic castration-resistant [[prostate cancer]] who have previously received [[Docetaxel (Taxotere)|docetaxel]]. ''(Based on AFFIRM)''
-*9/10/2014: FDA approved "for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC)" (no longer needed to be after docetaxel).
+*2014-09-10: Approved for the treatment of patients with metastatic castration-resistant [[prostate cancer]] (mCRPC). ''(No longer needs to be after docetaxel; based on PREVAIL and TERRAIN)''
+*2018-07-13: Approved for patients with [[Prostate cancer|castration-resistant prostate cancer (CRPC)]]. ''(No longer needs to be metatstatic; based on PROSPER<sub>PrCA</sub>)''
+*2019-12-16: Approved for patients with metastatic castration-sensitive [[prostate cancer]] (mCSPC). ''(No longer needs to be castration-resistant, if metastatic; based on ARCHES)''
+*2023-11-16: Approved for non-metastatic castration-sensitive [[prostate cancer]] (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). ''(No longer needs to be castration-resistant; based on EMBARK)''
+==History of changes in EMA indication==
+*2013-06-21: Initial marketing authorization as Xtandi. Xtandi is indicated for the treatment of adult men with metastatic castration-resistant [[prostate cancer]] whose disease has progressed on or after docetaxel therapy. ''(Based on AFFIRM)''
+*2014-11-28: Extension of indication for the treatment of adult men with metastatic castration-resistant [[prostate cancer]] who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.
+*2018-10-23: Extension of Indication to include adult men with high-risk non-metastatic castration-resistant [[prostate cancer]] (CRPC).
+*2021-04-30: Extension of Indication to include the treatment of adult men with metastatic hormonesensitive [[prostate cancer]] (mHSPC) for Xtandi in combination with androgen deprivation therapy. ''(Based on ARCHES)''
+==History of changes in Health Canada indication==
+*2013-05-29: Initial notice of compliance
+==History of changes in PMDA indication==
+*2014-03-24: Initial approval for the treatment of castration-resistant [[prostate cancer]].
+*2020-05-29: New indication for the treatment of metastatic [[prostate cancer]].
 ==Also known as==
-MDV3100.
+*'''Code name:''' MDV-3100
+*'''Brand names:''' Azel, Bdenza, Bnyx, Capmide, Enzamide, Glenza, Indenza, Xtandi
 ==References==
 <references/>
-[[Category:Drug index]]
+[[Category:Drugs]]
-[[Category:Antiandrogens]]
+[[Category:Oral medications]]
-[[Category:Androgen receptor inhibitors]]
+[[Category:Second-generation nonsteroidal antiandrogens]]
+[[Category:Breast cancer medications]]
 [[Category:Prostate cancer medications]]
-[[Category:Drugs FDA approved in 2012]]
+[[Category:EMA approved in 2013]]
+[[Category:FDA approved in 2012]]
+[[Category:Health Canada approved in 2013]]
+[[Category:PMDA approved in 2014]]
+[[Category:WHO Essential Cancer Medicine]]