A 36 year old woman with sarcoma was treated with a cumulative dose of 450 mg/m2 of doxorubicin. She presented with a drop in ejection fraction from 55% to 40% with exertional dyspnea and pedal edema. What has been shown to protect against doxorubicin-induced cardiotoxicity clinically?

  1. N-acetylcysteine
  2. Iron chelator
  3. Dexrazoxane
  4. Folic acid
  5. Vitamin E

Correct Answer: C

Rationale:

Reactive oxygen species generation and iron-mediated formation of hydroxyl radicals were thought to be the main mediators of anthracycline-induced cardiotoxicity (AIC). However, anti-oxidants or iron-chelators did not prevent AIC. It is now recognized that Topoisomerase 2b is the molecular mediator of AIC.

Dexrazoxane, an inhibitor of Topoisomerase 2, is the only FDA approved drug for AIC prevention.

References:

  1. Yeh E, Bickford CL, Cardiovascular Complications of Cancer Therapy: Incidence, Pathogenesis, Diagnosis and Management. JACC 2009; 0735-1097
  2. Zhang S, Bwa-Khalfe T, et al., Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature Magazine 2012, 10.1038/nm.2919

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