Introduction
Cabazitaxel is a second-generation semisynthetic taxane derivative approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Developed as a successor to docetaxel, cabazitaxel demonstrates activity in docetaxel-resistant tumors and represents an important therapeutic option in the advanced prostate cancer treatment landscape.
Mechanism of Action
Cabazitaxel binds to and stabilizes tubulin, promoting microtubule assembly and preventing depolymerization. This action leads to inhibition of mitotic spindle formation, cell cycle arrest in the G2/M phase, and ultimately apoptotic cell death. Unlike other taxanes, cabazitaxel demonstrates poor affinity for P-glycoprotein, allowing it to remain effective in multidrug-resistant cancer cells that overexpress this efflux transporter.
Indications
Cabazitaxel is FDA-approved for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing regimen. The European Medicines Agency has similarly approved cabazitaxel for mCRPC patients who have progressed during or after docetaxel therapy.
Dosage and Administration
Standard dosing: 20-25 mg/m² administered as a one-hour intravenous infusion every three weeks in combination with oral prednisone 10 mg daily Dose adjustments:- Hepatic impairment: Contraindicated if AST/ALT >1.5 × ULN or bilirubin >1 × ULN
- Renal impairment: No dosage adjustment necessary for mild to moderate impairment
- Hematologic toxicity: Dose reduction or delay based on neutrophil count
- Elderly patients: Close monitoring recommended due to increased susceptibility to adverse effects
Pharmacokinetics
Absorption: Administered intravenously with complete bioavailability Distribution: Extensive tissue distribution with high binding to human plasma proteins (89-92%) Metabolism: Primarily hepatic via CYP3A4/5 isoenzymes Elimination: Predominantly fecal excretion (76%) with minimal renal elimination (3.7%) Half-life: Terminal elimination half-life approximately 77 hoursContraindications
- History of severe hypersensitivity reaction to cabazitaxel or other taxanes
- Neutrophil count ≤1,500/mm³
- Severe hepatic impairment (total bilirubin > ULN or AST/ALT >1.5 × ULN)
- Pregnancy and breastfeeding
Warnings and Precautions
Boxed Warning:- Neutropenia-related deaths reported; frequent blood counts required
- Patients with high-risk clinical features should receive primary prophylaxis with G-CSF
- Hypersensitivity reactions requiring premedication and careful monitoring
- Gastrointestinal symptoms including nausea, vomiting, and diarrhea
- Renal failure, sometimes fatal, has been reported
- Elderly patients may be more susceptible to adverse effects
- Cardiovascular adverse events including arrhythmias and hypotension
Drug Interactions
Strong CYP3A inhibitors: Ketoconazole, itraconazole, clarithromycin, ritonavir - avoid concomitant use or consider dose reduction Strong CYP3A inducers: Rifampin, carbamazepine, phenytoin - may decrease cabazitaxel concentrations P-glycoprotein inhibitors: May increase cabazitaxel exposureAdverse Effects
Very common (≥10%):- Neutropenia (94%)
- Anemia (96%)
- Leukopenia (96%)
- Diarrhea (47%)
- Fatigue (37%)
- Nausea (34%)
- Peripheral neuropathy (14%)
- Febrile neutropenia (7%)
- Sepsis (5%)
- Severe hypersensitivity reactions
- Gastrointestinal perforation
- Renal failure
Monitoring Parameters
Prior to each cycle:- Complete blood count with differential
- Liver function tests
- Renal function tests
- Vital signs every 15 minutes during first infusion
- Monitor for hypersensitivity reactions
- Signs and symptoms of infection
- Neurological examination for peripheral neuropathy
- Gastrointestinal symptoms
- Hydration status
Patient Education
- Importance of compliance with premedication regimen
- Recognize signs of infection (fever, chills) and report immediately
- Manage diarrhea with appropriate hydration and antidiarrheal medications as directed
- Report symptoms of peripheral neuropathy (tingling, numbness, pain)
- Use effective contraception during treatment and for 3 months after
- Avoid grapefruit and grapefruit juice during treatment
- Maintain adequate hydration throughout treatment cycles
- Adhere to scheduled laboratory monitoring appointments
References
1. de Bono JS, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: the TROPIC study. Lancet. 2010;376(9747):1147-1154. 2. FDA Prescribing Information: Jevtana (cabazitaxel). Updated 2023. 3. National Comprehensive Cancer Network. Prostate Cancer Guidelines Version 2.2024. 4. Eisenberger M, et al. Phase III study of cabazitaxel versus mitoxantrone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel. J Clin Oncol. 2013;31(15_suppl):5018. 5. European Medicines Agency. Jevtana assessment report. EMA/501292/2014. 6. Corn PG, et al. Cabazitaxel for the treatment of metastatic castration-resistant prostate cancer. Future Oncol. 2021;17(15):1869-1881.