l NeuropathyIncludes peripheral motor neuropathy and peripheral sensory neuropathy. 50 (13%) 3 (< 1%) 12 (3.2%) 3 (< 1%)
Dysgeusia 41 (11%) 0 15 (4%) 0
Dizziness 30 (8%) 0 21 (6%) 2 (< 1%)
Headache 28 (8%) 0 19 (5%) 0
Renal and Urinary Tract Disorders
Hematuria 62 (17%) 7 (2%) 13 (4%) 1 (< 1%)
Dysuria 25 (7%) 0 5 (1%) 0
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea 43 (12%) 4 (1%) 16 (4%) 2 (< 1%)
Cough 40 (11%) 0 22 (6%) 0
Skin and Subcutaneous Tissue Disorders
Alopecia 37 (10%) 0 18 (5%) 0
Vascular Disorders
Hypotension 20 (5%) 2 (<1 %) 9 (2%) 1 (< 1%)
Median Duration of Treatment 6 cycles
4 cycles
Neutropenia and Associated Clinical Events:
Five patients experienced fatal infectious adverse events (sepsis or septic shock). All had grade 4 neutropenia and one had febrile neutropenia. One additional patient's death was attributed to neutropenia without a documented infection. Twenty-two (6%) patients discontinued JEVTANA treatment due to neutropenia, febrile neutropenia, infection, or sepsis. The most common adverse reaction leading to treatment discontinuation in the JEVTANA group was neutropenia (2%).
Hematuria:
Adverse events of hematuria, including those requiring medical intervention, were more common in JEVTANA-treated patients. The incidence of grade ≥ 2 hematuria was 6% in JEVTANA-treated patients and 2% in mitoxantrone-treated patients. Other factors associated with hematuria were well-balanced between arms and do not account for the increased rate of hematuria on the JEVTANA arm.
Hepatic Laboratory Abnormalities:
The incidences of grade 3–4 increased AST, increased ALT, and increased bilirubin were each ≤ 1%.
Elderly Population:
The following grade 1–4 adverse reactions were reported at rates ≥ 5% higher in patients 65 years of age or greater compared to younger patients: fatigue (40% vs. 30%), neutropenia (97% vs. 89%), asthenia (24% vs. 15%), pyrexia (15% vs. 8%), dizziness (10% vs. 5%), urinary tract infection (10% vs. 3%) and dehydration (7% vs. 2%), respectively.
The incidence of the following grade 3–4 adverse reactions were higher in patients ≥ 65 years of age compared to younger patients; neutropenia (87% vs. 74%), and febrile neutropenia (8% vs. 6%) [see Use in Specific Populations (8.5)].
No formal clinical drug-drug interaction trials have been conducted with JEVTANA.
Prednisone or prednisolone administered at 10 mg daily did not affect the pharmacokinetics of cabazitaxel.
CYP3A4 Inhibitors: Cabazitaxel is primarily metabolized through CYP3A [see Clinical Pharmacology (12.3)]. Though no formal drug interaction trials have been conducted for JEVTANA, concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) is expected to increase concentrations of cabazitaxel. Therefore, co-administration with strong CYP3A inhibitors should be avoided. Caution should be exercised with concomitant use of moderate CYP3A inhibitors.
CYP3A4 Inducers: Though no formal drug interaction trials have been conducted for JEVTANA, the co
