mitoxantrone (Novantrone, Mitozantrone)

Indications

• non-Hodgkin's lymphoma
• leukemia
  • FDA approved for acute non-lymphocytic leukemia
  • active against other leukemias as well
• advanced or recurrent breast cancer
• ovarian cancer
• prostate cancer
• pediatric sarcomas
• severe, progressive multiple sclerosis

Contraindications

• avoid in patients with pre-existing myelosuppression
• pregnancy

pregnancy category = d

Dosage

• solid tumors:
  • 12 mg/m2 IV every 4 weeks
  • 5 mg/m2 IV weekly for 3 weeks
• leukemia: 10-12 mg/m2/day for 3-5 days
• multiple sclerosis: every 3 month dosing for maximum of 8-12 doses

Stability:

• incompatible with heparin
• after penetration of stopper, stable for 7 days at room temperature or 14 days refrigerated

Injection: 2 mg/mL (10 mL, 12.5 mL, 15 mL).

Pharmacokinetics

• 95% is bound to plasma proteins
• retained in tissue
• metabolized by liver
• most is eliminated in the bile
• elimination 1/2life is 40 hours

elimination via liver

1/2life = 1 hour

elimination by hemodialysis = -

Monitor

• left-ventricular ejection fraction prior to each dose
• complete blood count (CBC)

Adverse effects

• common (> 10%)
  • coughing, shortness of breath, leukopenia, headache, blue-green discoloration of urine & sclera, alopecia nausea/vomiting, diarrhea, abdominal pain, mucositis, increased liver function tests, stomatitis, GI bleeding
• less common (1-10%)
  • hypotension, seizures, pruritus, skin desquamation, conjunctivitis, renal failure, jaundice, congestive heart failure
• uncommon (< 1%)
  • pain at site of injection
• other
  • emetic potential moderate (31-72%)
  • myelosuppression
    • WBC & platelets mild
    • onset 7-10 days
    • nadir 14 days
    • recovery 21 days
  • some alopecia
  • cardiomyopathy with cumulative dose
    • 160 mg/m2 cumulative dose
    • 125 mg/m2 in combination with anthracycline therapy
    • mediastinal irradiation also increases cardiotoxicity
    • less cardiotoxic than anthracyclines
  • fever
  • secondary acute myelogenous leukemia (AML)
  • increased risk of infection
  • menstrual irregularities
• black box warnings
  • cardiotoxicity
  • acute myeloid leukemia

Toxicity: no known antidote

Test interactions

increases serum K+

Mechanism of action

• antitumor antibiotic
• inhibits topoisomerase 2
• inhibits DNA synthesis
• not cell cycle-specific

More general terms

• antineoplastic agent (chemotherapeutic agent)
• enzyme inhibitor

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4212
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=51082