Introduction
Jevtana (cabazitaxel) is a second-generation microtubule inhibitor chemotherapy agent used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). It is a semisynthetic taxane derivative developed to overcome resistance to first-line taxane therapy. Jevtana received FDA approval in 2010 and represents an important therapeutic option for patients who have progressed following docetaxel-based chemotherapy.
Mechanism of Action
Cabazitaxel binds to and stabilizes tubulin, promoting microtubule assembly and preventing depolymerization. This action leads to inhibition of mitotic division between metaphase and anaphase, preventing cell proliferation and ultimately inducing apoptotic cell death in cancer cells. Unlike other taxanes, cabazitaxel is a poor substrate for the P-glycoprotein drug efflux pump, allowing it to remain effective in tumor cells that have developed multidrug resistance.
Indications
Jevtana is indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have previously been treated with a docetaxel-containing regimen.
Dosage and Administration
- Standard dosing: 25 mg/m² administered as a one-hour intravenous infusion every three weeks
- Premedication: Oral antihistamine (dexchlorpheniramine 5 mg or diphenhydramine 25 mg), corticosteroid (dexamethasone 8 mg or equivalent), and H2 antagonist administered at least 30 minutes prior to infusion
- Dosage adjustments: Required for hematologic toxicity, hepatic impairment, or severe adverse reactions
- Renal impairment: No dosage adjustment necessary for mild to moderate impairment
- Hepatic impairment: Contraindicated in patients with severe hepatic impairment (total bilirubin >3 × ULN)
Pharmacokinetics
- Absorption: Administered intravenously with complete bioavailability
- Distribution: Extensive tissue distribution with high binding to human plasma proteins (89-92%)
- Metabolism: Primarily hepatic metabolism via CYP3A4/5 isoenzymes
- Elimination: Primarily fecal elimination (76%) with renal excretion accounting for approximately 3.7% of administered dose
- Half-life: Terminal half-life of approximately 95 hours
Contraindications
- History of severe hypersensitivity reaction to cabazitaxel or polysorbate 80
- Neutrophil count ≤1,500/mm³
- Severe hepatic impairment (total bilirubin >3 × ULN)
- Pregnancy
Warnings and Precautions
- Myelosuppression: Severe neutropenia may occur; monitor blood counts frequently
- Hypersensitivity reactions: Can be severe and life-threatening; premedication required
- Gastrointestinal toxicity: Nausea, vomiting, and diarrhea may be severe
- Renal failure: Cases have been reported, primarily in patients with dehydration
- Pulmonary toxicity: Interstitial pneumonia/pneumonitis reported
- Elderly patients: Increased incidence of certain adverse reactions
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 exposure
- Other myelosuppressive agents: Additive myelosuppression risk
Adverse Effects
Common (≥10%):- Neutropenia (82%)
- Anemia (98%)
- Thrombocytopenia (48%)
- Diarrhea (47%)
- Fatigue (37%)
- Nausea (34%)
- Vomiting (22%)
- Constipation (22%)
- Anorexia (21%)
- Peripheral neuropathy (14%)
- Febrile neutropenia (7%)
- Severe hypersensitivity reactions
- Renal failure
- Severe diarrhea leading to dehydration and electrolyte imbalance
Monitoring Parameters
- Complete blood counts prior to each cycle and weekly during treatment
- Liver function tests at baseline and before each cycle
- Renal function monitoring
- Signs and symptoms of hypersensitivity reactions during infusion
- Neurological examination for peripheral neuropathy
- Hydration status and electrolyte balance
- Response assessment with PSA monitoring and radiographic evaluation
Patient Education
- Importance of premedication regimen compliance
- Signs and symptoms of infection (fever, chills) requiring immediate medical attention
- Management of gastrointestinal side effects with antiemetics and antidiarrheals
- Hydration importance, especially during episodes of diarrhea
- Potential for hair loss and other cosmetic side effects
- Need for reliable contraception during treatment
- Avoidance of grapefruit and grapefruit juice during treatment
- Reporting of new or worsening neurological symptoms
References
1. FDA Prescribing Information: Jevtana (cabazitaxel). 2021 2. 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 3. National Comprehensive Cancer Network (NCCN). Prostate Cancer Guidelines Version 2.2023 4. Oudard S, et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial-FIRSTANA. J Clin Oncol. 2017;35(28):3189-3197 5. Corn PG, et al. Cabazitaxel mechanisms of action and resistance in prostate cancer. Cancer Treat Rev. 2021;100:102283