Cabazitaxel

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Cabazitaxel
Cabazitaxel.png
Clinical data
Trade names Jevtana
Other namesXRP-6258
AHFS/Drugs.com Monograph
MedlinePlus a611009
License data
Pregnancy
category
  • AU:D
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Identifiers
  • (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(Acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl benzoate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.205.741 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C45H57NO14
Molar mass 835.944 g·mol−1
3D model (JSmol)
  • 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
  • InChI=1S/C45H57NO14/c1-24-28(57-39(51)33(48)32(26-17-13-11-14-18-26)46-40(52)60-41(3,4)5)22-45(53)37(58-38(50)27-19-15-12-16-20-27)35-43(8,36(49)34(55-10)31(24)42(45,6)7)29(54-9)21-30-44(35,23-56-30)59-25(2)47/h11-20,28-30,32-35,37,48,53H,21-23H2,1-10H3,(H,46,52)/t28-,29-,30+,32-,33+,34+,35-,37-,43+,44-,45+/m0/s1 X mark.svgN
  • Key:BMQGVNUXMIRLCK-OAGWZNDDSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. [5] It is a microtubule inhibitor, [3] and the fourth taxane to be approved as a cancer therapy.[ citation needed ]

Contents

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. [6] [7] [8] It is available as a generic medication. [9] [10]

Medical uses

Cabazitaxel is indicated in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer following docetaxel-based treatment. [3]

Mechanism of action

Taxanes enhance microtubule stabilization and inhibit cellular mitosis and division. [11] Moreover, taxanes prevent androgen receptor (AR) signaling by binding cellular microtubules and the microtubule-associated motor protein dynein, thus averting AR nuclear translocation. [12]

Clinical trials

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 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 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. [13] In a 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%). [14] Common adverse effects with cabazitaxel include neutropenia (including febrile neutropenia) and GIT side effects appeared mainly in diarrhea, whereas, neuropathy was rarely detected. [15]

Pharmacokinetics

Cabazitaxel administration causes a decrease in plasma concentrations showing triphasic kinetics: a mean half life (t1/2) of 2.6 min in the first phase, a mean t1/2 of 1.3 h in the second phase, and a mean t1/2 of 77.3 h in the third phase. [16]

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. [17]

References

  1. ↑ "Jevtana Product information". Health Canada . December 13, 2023. Retrieved February 17, 2025.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved October 22, 2023.
  3. 1 2 3 "Jevtana- cabazitaxel kit". DailyMed. Retrieved December 30, 2021.
  4. ↑ "Jevtana EPAR". European Medicines Agency (EMA). March 17, 2011. Retrieved August 10, 2024.
  5. ↑ "Cabazitaxel". NCI Drug Dictionary. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. February 2, 2011.
  6. ↑ "Drug Approval Package: Jevtana (Cabazitaxel) NDA #201023". U.S. Food and Drug Administration (FDA). July 8, 2013. Retrieved December 30, 2021.
  7. ↑ "Jevtana (cabazitaxel) Injection Approved by U.S. FDA After Priority Review" (Press release). Sanofi Aventis. June 17, 2010. Retrieved December 30, 2021– via PR Newswire.
  8. ↑ "Jevtana (cabazitaxel) Injection Approved by U.S. FDA After Priority Review - Jun 17, 2010" (Press release). Sanofi. June 17, 2010. Retrieved December 30, 2021.
  9. ↑ "Cabazitaxel: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved December 30, 2021.
  10. ↑ "First Generic Drug Approvals". U.S. Food and Drug Administration. October 17, 2022. Retrieved November 28, 2022.
  11. ↑ Jordan MA, Wilson L (April 2004). "Microtubules as a target for anticancer drugs". Nature Reviews. Cancer. 4 (4): 253–65. doi:10.1038/nrc1317. PMID   15057285. S2CID   10228718.
  12. ↑ Darshan MS, Loftus MS, Thadani-Mulero M, Levy BP, Escuin D, Zhou XK, et al. (September 2011). "Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer". Cancer Research. 71 (18): 6019–29. doi:10.1158/0008-5472.CAN-11-1417. PMC   3354631 . PMID   21799031.
  13. ↑ Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, et al. (October 2017). "Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA". Journal of Clinical Oncology. 35 (28): 3189–3197. doi:10.1200/JCO.2016.72.1068. PMID   28753384.
  14. ↑ "Cabazitaxel Effective for Hormone Refractory Prostate Cancer After Failure of Taxotere".[ permanent dead link ]
  15. ↑ Paller CJ, Antonarakis ES (March 2011). "Cabazitaxel: a novel second-line treatment for metastatic castration-resistant prostate cancer". Drug Design, Development and Therapy. 5: 117–24. doi: 10.2147/DDDT.S13029 . PMC   3063116 . PMID   21448449.
  16. ↑ Mita AC, Denis LJ, Rowinsky EK, Debono JS, Goetz AD, Ochoa L, et al. (January 2009). "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". Clinical Cancer Research. 15 (2): 723–30. doi: 10.1158/1078-0432.CCR-08-0596 . PMID   19147780.
  17. ↑ Tsao CK, Cutting E, Martin J, Oh WK (June 2014). "The role of cabazitaxel in the treatment of metastatic castration-resistant prostate cancer". Therapeutic Advances in Urology. 6 (3): 97–104. doi:10.1177/1756287214528557. PMC   4003844 . PMID   24883107.
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