FT is a 67-year-old male who was recently diagnosed with a rare form of cancer. The oncology team is deciding on an induction chemotherapy regimen among a number of various potential regimens. 

Allergies: NKDA

PMH: Hypertension, Hyperlipidemia, Type 2 Diabetes Mellitus, Myocardial infarction (2019), and heart failure with reduced ejection fraction (LVEF: 35%)

Medications: Lisinopril 20mg PO daily, Rosuvastatin 20mg PO daily, Metformin 1g PO BID, Aspirin 81mg PO daily, Metoprolol succinate 100mg PO once daily

The team asks your expertise regarding potential chemotherapeutics. Which of the following agents could potentially worsen his known cardiac conditions? Select all that apply. 

A. Doxorubicin

B. Methotrexate

C. Mitoxantrone

D. Etoposide

E. Dexrazoxane

Answer with rationale:

The correct answers are A and C.

The key to this question revolves upon recognizing the patient's significant cardiac history. His MI most likely contributed to his now reduced ejection heart failure which is significant when selecting chemotherapeutics. One would want to recognize any agents associated with cardiac toxicity. 

Doxorubicin (Adriamycin) is in the class of anthracyclines, a class known for their cardiotoxicity. Doxorubicin has a lifetime cumulative dose of 450-550 mg/m² for adults due to the increased risk of cardiotoxic effects above the 550mg/m² threshold. This toxicity manifests as cardiomyopathy and reduced left ventricular ejection fraction, making answer choice A correct.  Doxorubicin can also cause alopecia, nausea, vomiting, and can turn bodily fluids (urine, sweat, tears) an orange-ish color. 

Answer choice B is incorrect, as methotrexate is not commonly associated with cardiotoxicity. In very high doses, it can cause life-threatening immunosuppression requiring leucovorin administration to "rescue" the bone marrow. More commonly it is associated with mucositis and more typical global chemotherapy side effects although nausea and vomiting are less than many other agents. Keep in mind that methotrexate is often used in much lower doses for rheumatoid arthritis at doses of 2.5 up to 20mg once weekly. Misfills are common due to the weekly dosing regimen that gets filled as once daily which can lead to toxicity. 

Mitoxantrone (Novantrone) is another anthracycline, despite not having the common “-rubicin” suffix. Mitoxantrone also carries the risk of cardiotoxicity, although having less than doxorubicin, making answer choice C correct.

Etoposide (VP-16 or VePesid) is a plant alkaloid that works by a similar mechanism to anthracyclines, as they are both topoisomerase II inhibitors. Etoposide, however, does not lead to cardiotoxicity, making answer choice D incorrect. Instead, it can cause bone marrow suppression, abdominal pain, or hepatotoxicity.

Dexrazoxane (Zinecard or Totect) is a non-chemotherapy rescue agent to help prevent cardiotoxicity associated with anthracycline use, making answer choice E incorrect. The anthracycline should be administered within 30 minutes of the beginning of the dexrazoxane infusion.

Competencies Covered:

2.1 – Pharmacology, mechanism of action, or therapeutic class

2.3 – Boxed warnings or REMS

3.6 – Drug contraindications, allergies, or precautions

3.7 – Adverse drug effects, toxicology, or overdose