|Side effects||Low red blood cells, low white blood cells, low platelets, diarrhea|
|Chemical and physical data|
|Molar mass||835.944 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Cabazitaxel, sold under the brand name Jevtana, is a medication used to treat prostate cancer. Specifically it is used for metastatic castration-resistant prostate cancer who have failed other treatment. It is given by injection into a vein.
Common side effects include low red blood cells, low white blood cells, low platelets, and diarrhea. Other side effects may include allergic reactions and kidney problems. It is a taxane which interferes with microtubules.
Cabazitaxel was approved for medical use in the United States in 2010 and Europe in 2011. In the United Kingdom 60 mg costs the NHS about £3,700 as of 2021. This amount in the United States costs about 12,700 USD.
There are many questions about the optimal use of cabazitaxel after the approval of using it in the treatment of docetaxel-refractory mCRPC. One question is about the optimal use. Concerning the significant myelosuppression during cabazitaxel administration at 25 mg/m2, a randomized phase III study will appraise the safety and efficacy of cabazitaxel at 20 mg/m2. One more question is about the effectiveness and tolerability of cabazitaxel when it is administered with other therapies. A phase I/II trials are testing the co-administration of cabazitaxel with other therapies (e.g. abiraterone) and investigational agents (e.g. custirsen)
Common side effects include neutropenia (including febrile neutropenia) and GIT side effects appeared mainly in diarrhea, whereas, neuropathy was rarely detected.
Mechanism of action
Taxanes enhance the microtubules stabilization and inhibit the cellular mitosis and division. Moreover, taxanes prevent androgen receptor (AR) signaling by binding cellular microtubules and the microtubule-associated motor protein dynein, thus averting AR nuclear translocation.
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.
Cabazitaxel is basically 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.
In patients 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 patients with chemotherapy-naïve mCRPC. Cabazitaxel and docetaxel demonstrated different toxicity profiles, and C20 showed the overall lowest toxicity. In a phase III trial with 755 men for the treatment of castration-resistant prostate cancer, median survival was 15.1 months for patients receiving cabazitaxel versus 12.7 months for patients receiving mitoxantrone. Cabazitaxel was associated with more grade 3–4 neutropenia (81.7%) than mitoxantrone (58%).
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