Cabazitaxel: Difference between revisions

{{Short description|Chemical compound}}

{{Use mdy dates|date=November 2022}}

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{{Infobox drug

| verifiedrevid = 460123299

| width =

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<!-- Clinical data -->

| pronounce =

| tradename = Jevtana

| Drugs.com = {{drugs.com|monograph|cabazitaxel}}

| DailyMedID = Cabazitaxel

| pregnancy_AU = D

| pregnancy_AU_comment =

| routes_of_administration = [[Intravenous]]

| class =

| ATC_prefix = L01

| ATC_suffix = CD04

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

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| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

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| legal_NZ = <!-- Class A, B, C -->

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| legal_UK = POM

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref name="Jevtana FDA label">{{cite web | title=Jevtana- cabazitaxel kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de3d9c26-572b-4ea4-9b2d-dd58a2b3e8fa | access-date=December 30, 2021}}</ref>

| legal_EU = Rx-only

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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

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| legal_status = <!-- For countries not listed above -->

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| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 183133-96-2

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| IUPHAR_ligand = 6798

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| UNII_Ref = {{fdacite|correct|FDA}}

| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = D09755

| KEGG2 = D10452

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 63584

| ChEMBL = 1201748

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| PDB_ligand =

| synonyms = XRP-6258

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| IUPAC_name = (1''S'',2''S'',3''R'',4''S'',7''R'',9''S'',10''S'',12''R'',15''S'')-4-(Acetyloxy)-15-<nowiki/>{[(2''R'',3''S'')-3-<nowiki/>{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^3,10.0^4,7]heptadec-13-en-2-yl benzoate

| SMILES = CO[C@H]1C[C@H]2OC[C@@]2(OC(C)=O)[C@H]2[C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)c4ccccc4)C(C)=C([C@@H](OC)C(=O)[C@]12C)C3(C)C

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'''Cabazitaxel''', sold under the brand name '''Jevtana''', is a semi-synthetic derivative of a natural [[taxoid]].<ref>{{cite web | title = Cabazitaxel | url = http://www.cancer.gov/drugdictionary/?CdrID=534131 | work = NCI Drug Dictionary | publisher = U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute|date = February 2, 2011}}</ref> It is a [[microtubule]] inhibitor,<ref name="Jevtana FDA label" /> and the fourth [[taxane]] to be approved as a [[cancer therapy]].{{citation needed|date=December 2021}}

Cabazitaxel was developed by [[Sanofi-Aventis]] and was approved by the US [[Food and Drug Administration]] (FDA) for the treatment of hormone-refractory [[prostate cancer]] in June 2010.<ref>{{cite web | title=Drug Approval Package: Jevtana (Cabazitaxel) NDA #201023 | website=U.S. [[Food and Drug Administration]] (FDA) | date=July 8, 2013 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000TOC.cfm | access-date=December 30, 2021 }}</ref><ref>{{cite press release | title=Jevtana (cabazitaxel) Injection Approved by U.S. FDA After Priority Review | publisher=Sanofi Aventis | via=PR Newswire | date=June 17, 2010 | url=https://www.prnewswire.com/news-releases/jevtana-cabazitaxel-injection-approved-by-us-fda-after-priority-review-96589609.html | access-date=December 30, 2021}}</ref><ref>{{cite press release | title=Jevtana (cabazitaxel) Injection Approved by U.S. FDA After Priority Review - Jun 17, 2010 | publisher=Sanofi | date=June 17, 2010 | url=https://www.news.sanofi.us/press-releases?item=118525 | access-date=December 30, 2021}}</ref> It is available as a [[generic medication]].<ref>{{cite web | title=Cabazitaxel: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=207949 | access-date=December 30, 2021}}</ref><ref>{{cite web | title=First Generic Drug Approvals | website=U.S. Food and Drug Administration | date=October 17, 2022 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | access-date=November 28, 2022}}</ref>

== Medical uses ==

Cabazitaxel is [[Indication (medicine)|indicated]] in combination with [[prednisone]] for the treatment of metastatic castration-resistant [[prostate cancer]] following [[docetaxel]]-based treatment.<ref name="Jevtana FDA label" />

== Mechanism of action ==

Taxanes enhance microtubule stabilization and inhibit cellular mitosis and division.<ref>{{cite journal | vauthors = Jordan MA, Wilson L | title = Microtubules as a target for anticancer drugs | journal = Nature Reviews. Cancer | volume = 4 | issue = 4 | pages = 253–65 | date = April 2004 | pmid = 15057285 | doi = 10.1038/nrc1317 | s2cid = 10228718 }}</ref> Moreover, taxanes prevent androgen receptor (AR) signaling by binding cellular microtubules and the microtubule-associated motor protein dynein, thus averting AR nuclear translocation.<ref>{{cite journal | vauthors = Darshan MS, Loftus MS, Thadani-Mulero M, Levy BP, Escuin D, Zhou XK, Gjyrezi A, Chanel-Vos C, Shen R, Tagawa ST, Bander NH, Nanus DM, Giannakakou P | title = Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer | journal = Cancer Research | volume = 71 | issue = 18 | pages = 6019–29 | date = September 2011 | pmid = 21799031 | pmc = 3354631 | doi = 10.1158/0008-5472.CAN-11-1417 }}</ref>

In people with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is markedly enhanced with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA (ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20&nbsp;mg/m² (C20) or 25&nbsp;mg/m² (C25) is superior to docetaxel 75&nbsp;mg/m² (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. However, C20 and C25 did not demonstrate superiority for OS versus D75 in people with chemotherapy-naïve mCRPC. Cabazitaxel and docetaxel demonstrated different toxicity profiles, and C20 showed the overall lowest toxicity.<ref name="ascopubs.org">{{cite journal | vauthors = Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, Hjälm-Eriksson M, Jassem J, Thiery-Vuillemin A, Caffo O, Castellano D, Mainwaring PN, Bernard J, Shen L, Chadjaa M, Sartor O | title = Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA | journal = Journal of Clinical Oncology | volume = 35 | issue = 28 | pages = 3189–3197 | date = October 2017 | pmid = 28753384 | doi = 10.1200/JCO.2016.72.1068 }}</ref>

In a [[Phases of clinical research#Phase III|phase III trial]] with 755 men for the treatment of [[castration-resistant prostate cancer]], median survival was 15.1 months for participants receiving cabazitaxel versus 12.7 months for participants receiving [[mitoxantrone]]. Cabazitaxel was associated with more grade 3–4 [[neutropenia]] (81.7%) than mitoxantrone (58%).<ref>{{cite web |url=http://professional.cancerconsultants.com/oncology_main_news.aspx?id=44709 |title=Cabazitaxel Effective for Hormone Refractory Prostate Cancer After Failure of Taxotere }}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Common adverse effects with cabazitaxel include neutropenia (including febrile neutropenia) and GIT side effects appeared mainly in diarrhea, whereas, neuropathy was rarely detected.<ref name="ncbi.nlm.nih.gov">{{cite journal | vauthors = Paller CJ, Antonarakis ES | title = Cabazitaxel: a novel second-line treatment for metastatic castration-resistant prostate cancer | journal = Drug Design, Development and Therapy | volume = 5 | pages = 117–24 | date = March 2011 | pmid = 21448449 | pmc = 3063116 | doi = 10.2147/DDDT.S13029 | doi-access = free }}</ref>

== Pharmacokinetics ==

Cabazitaxel administration causes a decrease in plasma concentrations showing triphasic kinetics: a mean half life (t_1/2) of 2.6 min in the first phase, a mean t_1/2 of 1.3 h in the second phase, and a mean t_1/2 of 77.3 h in the third phase.<ref>{{cite journal | vauthors = Mita AC, Denis LJ, Rowinsky EK, Debono JS, Goetz AD, Ochoa L, Forouzesh B, Beeram M, Patnaik A, Molpus K, Semiond D, Besenval M, Tolcher AW | title = Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors | journal = Clinical Cancer Research | volume = 15 | issue = 2 | pages = 723–30 | date = January 2009 | pmid = 19147780 | doi = 10.1158/1078-0432.CCR-08-0596 | doi-access = free }}</ref>

=== Metabolism ===

Cabazitaxel is metabolized in the liver by [cytochrome P₄₅₀ (CYP)3A4/5 > CYP2C8], which result in seven plasma metabolites and excreted 20 metabolites. During 14 days after administration, 80% of cabazitaxel is excreted: 76% in the feces and 3.7% as a renal excretion.<ref name=":0">{{cite journal | vauthors = Tsao CK, Cutting E, Martin J, Oh WK | title = The role of cabazitaxel in the treatment of metastatic castration-resistant prostate cancer | journal = Therapeutic Advances in Urology | volume = 6 | issue = 3 | pages = 97–104 | date = June 2014 | pmid = 24883107 | pmc = 4003844 | doi = 10.1177/1756287214528557 }}</ref>

== References ==

* {{cite web | title=Cabazitaxel Accord 20 mg/mL concentrate for solution infusion: Risk of medication errors and mix-up with Jevtana (60 mg/1.5 mL) solvent infusion | website=[[European Medicines Agency]] (EMA) | date=October 28, 2020 | url=https://www.ema.europa.eu/en/medicines/dhpc/cabazitaxel-accord-20-mgml-concentrate-solution-infusion-risk-medication-errors-mix-jevtana-60-mg15 }}

* {{ClinicalTrialsGov|NCT00417079|XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC)}}

* {{ClinicalTrialsGov|NCT01308580|Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer (PROSELICA)}}

* {{ClinicalTrialsGov|NCT02485691|Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)}}

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[[Category:Benzoate esters]]

[[Category:Taxanes]]

[[Category:Tert-Butyl esters]]