| Verifiedfields: | changed |
| Watchedfields: | changed |
| Verifiedrevid: | 460123299 |
| Tradename: | Jevtana |
| Dailymedid: | Cabazitaxel |
| Pregnancy Au: | D |
| Routes Of Administration: | Intravenous |
| Atc Prefix: | L01 |
| Atc Suffix: | CD04 |
| Legal Au: | S4 |
| Legal Uk: | POM |
| Legal Us: | Rx-only |
| Legal Us Comment: | [1] |
| Legal Eu: | Rx-only |
| Legal Eu Comment: | [2] |
| Cas Number: | 183133-96-2 |
| Pubchem: | 9854073 |
| Iuphar Ligand: | 6798 |
| Drugbank: | DB06772 |
| Chemspiderid: | 8029779 |
| Unii: | 51F690397J |
| Kegg: | D09755 |
| Kegg2: | D10452 |
| Chebi: | 63584 |
| Chembl: | 1201748 |
| Synonyms: | XRP-6258 |
| Iupac Name: | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(Acetyloxy)-15- |
| C: | 45 |
| H: | 57 |
| N: | 1 |
| O: | 14 |
| 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 |
| Stdinchi: | 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 |
| Stdinchikey: | BMQGVNUXMIRLCK-OAGWZNDDSA-N |
Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid.[3] It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.
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.[4] [5] [6] It is available as a generic medication.[7] [8]
Cabazitaxel is indicated in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer following docetaxel-based treatment.
Taxanes enhance microtubule stabilization and inhibit cellular mitosis and division.[9] Moreover, taxanes prevent androgen receptor (AR) signaling by binding cellular microtubules and the microtubule-associated motor protein dynein, thus averting AR nuclear translocation.[10]
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.[11] 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%).[12] Common adverse effects with cabazitaxel include neutropenia (including febrile neutropenia) and GIT side effects appeared mainly in diarrhea, whereas, neuropathy was rarely detected.[13]
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.[14]
Cabazitaxel is metabolized in the liver by [cytochrome P<sub>450</sub> (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.[15]