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Action/Kinetics:
Most active in the late S phase of cell division but is not cell-cycle specific. Appears to bind to DNA by intercalation between base pairs and a nonintercalative electrostatic interaction, causing an inhibition of DNA and RNA synthesis. Low distribution to the brain, spinal cord, spinal fluid, and eyes.
t
1/2: Approximately 6 days. Highly bound to plasma proteins. Excreted through both the feces (via the bile) and the urine (up to 65% unchanged).
Uses:
In combination with other drugs, for the initial treatment of acute nonlymphocytic leukemias, including monocytic, promyelocytic, myelocytic, and acute erythroid leukemias. In combination with steroids to treat pain from advanced hormone-refractory prostate cancer.
Investigational: Alone or in combination with other drugs to treat breast and liver cancer; non-Hodgkin's lymphomas.
Contraindications:
Preexisting myelosuppression (unless benefits outweigh risks). Lactation. Intrathecal use.
Special Concerns:
Safety and efficacy have not been established in children. May be mutagenic.
Side Effects:
Hematologic: Severe myelosuppression, ecchymosis, petechiae.
GI: N&V;, diarrhea, stomatitis, mucositis, abdominal pain, GI bleeding.
CNS: Headache, seizures.
CV: CHF, decreases in LV ejection fraction, arrhythmias, tachycardia, chest pain, hypotension.
Respiratory: Cough, dyspnea.
Miscellaneous: Conjunctivitis, urticaria, rashes, renal failure, hyperuricemia, alopecia, fever, phlebitis (at infusion site), tissue necrosis (as a result of extravasation), jaundice. In addition, there is an increased risk of pneumonia, urinary tract and fungal infections, and sepsis.
Laboratory Test Alterations:
Transient
AST and ALT.
Overdose Management:
Symptoms: Severe leukopenia with infection.
Treatment: Antibiotic therapy. Monitor hematology.
How Supplied:
Injection: 2 mg/mL
Dosage
?IV Infusion
Initial therapy for acute nonlymphocytic leukemia, induction.
Mitoxantrone, 12 mg/m
2/day on days 1-3 combined with cytosine arabinoside, 100 mg/m
2 as a continuous 24-hr infusion on days 1-7. If the response is incomplete, a second induction course may be given using the same daily dosage, but giving mitoxantrone for 2 days and cytosine arabinoside for 5 days.
Consolidation therapy, approximately 6 weeks after final induction therapy: mitoxantrone, 12 mg/m
2/day on days 1 and 2 combined with cytosine arabinoside, 100 mg/m
2 as a continuous 24-hr infusion on days 1-5. A second consolidation course of therapy may be given 4 weeks after the first.
