A 17-year-old on multi-agent chemotherapy for osteosarcoma is receiving doxorubicin. Cumulative cardiotoxicity limits the total lifetime dose to approximately:

• A 100 mg/m²
• B 250 mg/m²
• C 550 mg/m² ✓
• D 1200 mg/m²

Explanation

Doxorubicin causes dose-dependent, usually irreversible cardiomyopathy through free radical injury to cardiac myocytes. The accepted cumulative ceiling is around 450 to 550 mg/m², above which the incidence of clinical heart failure rises steeply. Serial echocardiography or MUGA scanning monitors ejection fraction during therapy. The lower figures would terminate osteosarcoma regimens prematurely, and dexrazoxane is sometimes used for cardioprotection when exposure must exceed the limit.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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