OnCo
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Caution: cumulative anthracycline dose and the heart

Every dose of doxorubicin adds to a lifetime total; above roughly 450 mg/m2 heart failure risk rises steeply, so sarcoma and lymphoma regimens are capped and hearts are monitored.

Cardiomyopathy incidence ~5% at 400 mg/m2, ~26% at 550 mg/m2; risk higher with chest radiotherapy, trastuzumab, age extremes. Dexrazoxane, liposomal doxorubicin, continuous infusion, and echocardiographic surveillance mitigate.

Rationale
Topoisomerase IIβ-mediated cardiomyocyte damage is dose-dependent and irreversible.
Evidence
Decades of cohort data; dexrazoxane RCTs.

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