Usual Adult Dose for Acute Lymphoblastic Leukemia

18 to less than 22 years:
52 mg/m2 IV over 2 hours daily for 5 consecutive days of a 28-day cycle; repeat every 2 to 6 weeks

Comments:

• Subsequent cycles should begin no sooner than 14 days from day 1 of the previous cycle.
• Subsequent cycles may be administered when the ANC is greater than or equal to 750/mm3.
• Provide supportive care, such as IV fluids, antihyperuricemics, and alkalinization of urine throughout therapy to reduce the risk of tumor lysis and other adverse events.
• Monitor renal, hepatic, and cardiac function during therapy.
• Monitor patients taking medications known to affect blood pressure.
• Discontinue therapy if hypotension develops during the 5 days of administration.

Use: For patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least 2 prior regimens

Usual Pediatric Dose for Acute Lymphoblastic Leukemia

1 year and older:
52 mg/m2 IV over 2 hours daily for 5 consecutive days of a 28-day cycle; repeat every 2 to 6 weeks

Comments:

• Subsequent cycles should begin no sooner than 14 days from day 1 of the previous cycle.
• Subsequent cycles may be administered when the ANC is greater than or equal to 750/mm3.
• Provide supportive care, such as IV fluids, antihyperuricemics, and alkalinization of urine throughout therapy to reduce the risk of tumor lysis and other adverse events.
• Monitor renal, hepatic, and cardiac function during therapy.
• Monitor patients taking medications known to affect blood pressure.
• Discontinue therapy if hypotension develops during the 5 days of administration.

Use: For patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least 2 prior regimens

Renal Dose Adjustments

• Mild renal dysfunction (CrCl 60 to less than 90 mL/min): No adjustment recommended.
• Moderate renal dysfunction (CrCl 30 to less than 60 mL/min): Reduce the starting dose by 50%.
• Severe renal dysfunction (CrCl less than 15 to less than 30 mL/min) and end stage renal disease (CrCl less than 15 mL/min): Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Supportive Medications and Medications to Avoid:

• Consider prophylactic antiemetic medications as this drug is moderately emetogenic.
• Consider the use of prophylactic steroids to mitigate Systemic Inflammatory Response Syndrome (SIRS) or capillary leak syndrome (e.g., hypotension, tachycardia, tachypnea, pulmonary edema).
• Minimize exposure to drugs with known renal toxicity during the 5 days of therapy since the risk of renal toxicity may be increased.
• Consider avoiding concomitant use of medications known to induce hepatic toxicity.

Dose Modifications and Reinitiation of Therapy:
HEMATOLOGIC TOXICITY:

• Administer subsequent cycles no sooner than 14 days from the starting day of the previous cycle and provided the patient ANC is 0.75 x 10(9)/L or greater.
• If a patient experiences a Grade 4 neutropenia (ANC less than 0.5 x 10(9)/L) lasting 4 weeks or more, reduce dose by 25% for the next cycle.

NONHEMATOLOGIC TOXICITY:

• Withhold therapy if the patient develops a clinically significant infection, until the infection is controlled, then restart at the full dose.
• Withhold therapy for Grade 3 noninfectious nonhematologic toxicity (excluding transient elevations in serum transaminases and/or serum bilirubin and/or nausea/vomiting controlled by antiemetic therapy); reinstitute therapy at a 25% dose reduction with resolution or return to baseline.
• Discontinue therapy for Grade 4 noninfectious nonhematologic toxicity.
• Discontinue therapy if a patient shows early signs or symptoms of SIRS or capillary leak (e.g., hypotension, tachycardia, tachypnea, pulmonary edema) occur and provide supportive measures.
• Discontinue therapy if Grade 3 or higher increases in creatinine or bilirubin are noted; reinstitute therapy at a 25% dose reduction, when the patient is stable and organ function has returned to baseline. If hyperuricemia is anticipated (tumor lysis), initiate measures to control uric acid.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 1 year or older than 21 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Therapy should be initiated and supervised by a physician experienced in the management of patients with acute leukemia.

Storage requirements:

• Store diluted product at room temperature (15C to 30C).

Reconstitution/preparation techniques:

• Filter through a sterile 0.2-micron syringe filter and dilute with 5% dextrose injection or 0.9% sodium chloride injection prior to IV infusion to a final concentration between 0.15 and 0.4 mg/mL.
• Use within 24 hours of preparation.

IV compatibility:

• Do not administer any other medications through the same IV line.