Advanced Disease Regimen: Cabazitaxel + Prednisone
de Bono JS et al. Lancet 2010;376:1147–1154
Note: Severe hypersensitivity reactions can occur with cabazitaxel administration. These may include generalized rash/erythema, hypotension, and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of cabazitaxel infusion and administration of appropriate therapy. Patients should receive primary prophylaxis against hypersensitivity reactions as described below. Cabazitaxel must not be given to patients who have a history of severe hypersensitivity reactions to other drugs formulated with polysorbate 80, such as fosaprepitant dimeglumine (the parenteral formulation of aprepitant [Emend]), darbepoetin alfa, docetaxel, etoposide, recombinant human papillomavirus quadrivalent vaccine (Gardasil), and various vaccines. Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the cabazitaxel infusion, thus facilities and equipment for the treatment of hypotension and bronchospasm should be available
Premedication:
At least 30 minutes prior to each cabazitaxel dose, administer the following medications to reduce the risk and/or severity of hypersensitivity:
Diphenhydramine 25 mg, or an equivalent H1-receptor antihistamine, orally or intravenously
Dexamethasone 8 mg or an equipotent glucocorticoid
Ranitidine 50 mg intravenously or 150 mg orally, or an equivalent histamine (H2)-receptor antagonist
Cabazitaxel 25 mg/m2 intravenously over 60 minutes, diluted in a volume of 0.9% sodium chloride injection or 5% dextrose injection sufficient to produce a solution with concentration within the range 0.1–0.26 mg/mL, on day 1, every 3 weeks (total dosage/cycle = 25 mg/m2)
Prednisone 10 mg/day orally, continually for 21 consecutive days (total dose/21-day cycle = 210 mg)
Note:
Cabazitaxel is extensively metabolized in the liver (>95%), primarily by cytochrome P450 (CYP) CYP3A4/5 enzymes (80–90%), and, to a lesser extent, by the polymorphically expressed enzyme, CYP2C8. Consequently hepatic impairment is likely to increase cabazitaxel concentrations
Although no formal drug interaction trials with cabazitaxel have been conducted, clinicians should use caution with respect to the following:
CYP3A4 inhibitors: Concomitant administration of strong CYP3A subfamily inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) is expected to increase concentrations of cabazitaxel. Therefore, coadministration with strong CYP3A inhibitors should be avoided. Caution should be exercised with concomitant use of moderate CYP3A subfamily inhibitors
CYP3A4 inducers: The concomitant administration of strong CYP3A subfamily inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine, rifampin) is expected to decrease cabazitaxel concentrations. Therefore, coadministration with strong CYP3A inducers should be avoided. In addition, patients should also refrain from taking St. John's wort
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is LOW
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Patient Population Studied
A study of 755 patients with pathologically proven castration-refractory prostate cancer with documented disease progression during or after completion of docetaxel treatment. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0–2. Patients with measurable disease were required to have documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with at least 1 metastatic visceral or soft-tissue lesion. Patients with nonmeasurable disease were required to have rising serum prostate-specific antigen (PSA) concentrations (at least 2 consecutive increases relative to a reference value measured at least a week apart) or the appearance of at least 1 new demonstrable radiographic lesion. Additional inclusion criteria were: previous and ongoing castration by orchiectomy, LHRH agonists, or both interventions