| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Cabazitaxel | 20 mg/m2 IV* | Dilute in 250 mL NS or D5W¶ and administer over one hour; special equipment and preparation techniques neededΔ. | Day 1 |
| Prednisone | 10 mg orally | Daily. | Days 1 to 21 |
| Pretreatment considerations: |
| Emesis risk | - MODERATE (>30 to 90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Severe hypersensitivity reactions may occur. Cabazitaxel is contraindicated in patients with a prior history of hypersensitivity to other drugs formulated with polysorbate 80. All patients should receive IV premedication with a corticosteroid (dexamethasone 8 mg or equivalent), an H1 receptor antagonist (diphenhydramine 25 mg or an equivalent), and an H2 receptor antagonist (famotidine 20 mg or equivalent) at least 30 minutes prior to cabazitaxel administration.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Infection prophylaxis | - Primary prophylaxis with G-CSF is not recommended for all patients (risk of febrile neutropenia 8%[1]). However, primary prophylaxis with G-CSF should be considered for all patients with high-risk clinical features: Age >65 years, poor performance status, previous episodes of febrile neutropenia, extensive prior radiation, poor nutritional status, or other serious comorbidities. Bone marrow suppression is prominent with cabazitaxel, and deaths due to neutropenia are reported.
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
|
| Dose adjustment for baseline liver or renal dysfunction | - Reduce cabazitaxel dose for mild to moderate hepatic impairment. Cabazitaxel is not recommended in patients with severe hepatic impairment (total bilirubin >3 times ULN). Cabazitaxel should be used with caution in patients with severe renal insufficiency requiring hemodialysis.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents.
|
| Dose adjustment for known drug interactions | - Concurrent cabazitaxel administration with strong CYP3A4 inhibitors should be avoided due to potentially increased cabazitaxel plasma concentrations.
- If coadministration of cabazitaxel and a strong CYP3A4 inhibitor(s) is unavoidable, reduce cabazitaxel dose by 25%.
|
| Monitoring parameters: |
- CBC with differential weekly during the first cycle and at the start of each subsequent treatment cycle.
|
- Renal and liver function testing at least every three weeks during treatment.
|
- Monitor neurologic function and gastrointestinal toxicities prior to each treatment cycle.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Do not give if neutrophil count is ≤1500/microL. For prolonged grade 3 or 4 neutropenia (greater than one week) despite appropriate medication including G-CSF for febrile neutropenia, delay treatment until improvement/resolution and neutrophil count is >1500/microL, then reduce dose to 20 mg/m2. Use G-CSF for secondary prophylaxis.[2] Discontinue cabazitaxel if these toxicities recur at the lower dose level.
|
| Gastrointestinal toxicity | - For grade 3 or higher diarrhea or persisting diarrhea despite appropriate medication and fluid and electrolyte replacement, delay treatment until improvement or resolution, then reduce dose to 20 mg/m2. For persistent diarrhea despite dose reduction, discontinue cabazitaxel therapy.[2]
|
| Peripheral neuropathy | - For grade 2 peripheral neuropathy, delay treatment until improvement/resolution, then reduce dose to 20 mg/m2.[2] Discontinue cabazitaxel for grade 3 or grade 4 peripheral neuropathy.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
