Usual Adult Dose for Prostate Cancer

20 mg/m2 IV over one-hour every three weeks

• Some patients may received a dose of 25 mg/m2 every three weeks

Comments:

• In selected patients, the dose may be increased to 25 mg/m2; primary prophylaxis with G-CSF is recommended in these patients.
• Use in combination with oral prednisone 10 mg once a day.
• Dose is based on calculation of the Body Surface Area (BSA).
• Give premedication regimen at least 30 minutes prior to each administration, including antiemetics prophylaxis as needed.
• Ensure adequate hydration throughout treatment.

Use: In combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen

Renal Dose Adjustments

CrCl 15 mL/min to less than 90 mL/min not requiring hemodialysis: No adjustment necessary
End stage renal dysfunction (CrCl less than 15 mL/min): Use with caution and monitor carefully during treatment.

Liver Dose Adjustments

Mild hepatic dysfunction (total bilirubin greater than 1 to 1.5 times upper limit of normal [x ULN] or AST greater than 1.5 x ULN): Maximum dose 20 mg/m2
Moderate hepatic dysfunction (total bilirubin greater than 1.5 to 3 x ULN and any AST): Maximum tolerated dose 15 mg/m2; however, efficacy of this dose is unknown
Severe hepatic dysfunction (total bilirubin greater than 3 x ULN): Contraindicated

Dose Adjustments

Dose modifications:

• Patients at a 20 mg/m2 dose who require dose reduction should decrease dosage to 15 mg/m2
• Patients at a 25 mg/m2 dose who require dose reduction should decrease dosage to 20 mg/m2
• One additional dose reduction to 15 mg/m2 may be considered

Adjust dosage for the following adverse events:

• Prolonged (more than 1 week) Grade 3 or higher neutropenia despite appropriate medication including G-CSF: Delay treatment until neutrophil count is greater than 1,500 cells/mm3, then reduce dose by one dose level. Use G-CSF for secondary prophylaxis.
• Febrile neutropenia or neutropenic infection: Delay treatment until improvement or resolution, and neutrophil count is greater than 1,500 cells/mm3, then reduce dose by one dose level.
• Grade 3 or higher, or persisting diarrhea despite appropriate medication, fluid, and electrolytes replacement: Delay treatment until improvement or resolution, then reduce dose by one dose level.
• Grade 2 peripheral neuropathy: Delay treatment until improvement or resolution, then reduce dose by one dose level.
• Grade 3 or higher peripheral neuropathy: Discontinue treatment.

Adjust dosage for use with strong CYP450 3A inhibitors:

• Avoid the coadministration of strong inhibitors of CYP450 3A drugs.
• If concomitant use of strong inhibitors of CYP450 3A drugs is inevitable, consider a cabazitaxel 25% dose reduction.

Precautions

US BOXED WARNINGS:
NEUTROPENIA:

• Neutropenic deaths have been reported.
• Monitor for neutropenia with frequent blood cell counts.
• Do not give this drug to patients with neutrophil counts of 1500 cells/mm3 or less.
• Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
• Consider primary prophylaxis with G-CSF in all patients receiving a dose of 25 mg/m2.

HYPERSENSITIVITY:

• Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm.
• Severe hypersensitivity reactions require immediate discontinuation of the infusion and administration of appropriate therapy.
• Patients should receive premedication.
• Do not give this drug to patients who have a history of severe hypersensitivity reactions to this drug or to other drugs formulated with polysorbate 80.

CONTRAINDICATIONS:

• Neutrophil counts of 1500/mm3 or less
• History of severe hypersensitivity reactions to this drug or to other drugs formulated with polysorbate 80
• Severe hepatic impairment (total bilirubin greater than 3 times ULN)

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer this drug as a one-hour IV infusion.
• This drug requires two dilutions prior to administration.
• Do not use PVC infusion containers for preparation or infusion.
• Do not use polyurethane infusion sets for administration.
• Use an in-line 0.22 micrometer filter during administration.

Storage requirements:

• Unopened: Store at room temperature; do not refrigerate
• Reconstituted solutions: Use within 8 hours at room temperature OR 24 hours under refrigeration; includes the 1-hour infusion time

Reconstitution/preparation techniques: The manufacturer product information should be consulted.

IV compatibility: Do not mix with other medications.

General:

• Administer under the supervision of a physician experienced in the use of antineoplastics.
• Facilities and equipment for the treatment of serious hypersensitivity reactions, like hypotension and bronchospasm, must be available.

Monitoring:

• Hematologic: Neutropenia with frequent blood cell counts
• Genitourinary: Monitor of cystitis
• Pulmonary: Monitor for new or worsening pulmonary symptoms

Patient advice:

• Educate patients about risk of hypersensitivity and to immediately report signs of hypersensitivity reactions.
• Explain the importance of routine blood cell counts.
• Have patients monitor their temperature frequently and immediately report fever.
• Explain the importance of taking corticosteroids as instructed.
• Inform patients of infection, dehydration, and renal failure risk; instruct patients to immediately report fever, significant vomiting or diarrhea, decreased urinary output, and hematuria.