An adolescent on neoadjuvant chemotherapy for osteosarcoma receives doxorubicin as part of the MAP regimen. Serial assessment of left ventricular ejection fraction is performed before each cycle. What cumulative dose of doxorubicin marks the threshold above which irreversible congestive cardiomyopathy risk rises steeply?

• A 150 mg per square metre
• B 300 mg per square metre
• C 550 mg per square metre ✓
• D 800 mg per square metre

Explanation

Doxorubicin produces a dose-dependent, often irreversible dilated cardiomyopathy. Risk rises sharply above a cumulative dose of approximately 450 to 550 mg per square metre, which is why total lifetime dosing is capped near this figure. Serial echocardiography or radionuclide angiography monitors ejection fraction during therapy. Children are more vulnerable, and late cardiomyopathy is a recognised long-term survivorship problem in osteosarcoma protocols.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

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