Cycle length: 21 days. Duration of therapy: 6 to 8 cycles.* |
Drug | Dose and route | Administration | Given on days |
Fluorouracil (FU) | 500 mg/m2 IV | Drug is available in 50 mg/mL solution that needs no further dilution prior to administration as IV push. | Day 1 |
Epirubicin | 100 mg/m2 IV¶ | Administer into a free-flowing IV solution with NS,Δ generally over 3 to 20 minutes. | Day 1 |
Cyclophosphamide | 500 mg/m2 IV | Dilute with 250 NS or D5WΔ and administer over 30 to 60 minutes. | Day 1 |
Pretreatment considerations: |
Hydration | - Patients receiving cyclophosphamide should maintain adequate oral hydration (2 to 3 L/day) and void frequently to reduce risk of hemorrhagic cystitis.[2]
- Refer to UpToDate topics on hemorrhagic cystitis in cancer patients.
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Emesis risk | - HIGH (>90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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Vesicant/irritant properties | - Epirubicin is a vesicant, FU and cyclophosphamide are irritants; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated.[1]
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
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Dose adjustment for baseline liver or kidney dysfunction | - A lower starting dose of FU may be needed for patients with liver impairment. A lower starting dose of cyclophosphamide may be needed in patients with kidney impairment. A lower starting dose of epirubicin may be needed in patients with kidney or hepatic impairment.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney insufficiency, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
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Cardiac issues | - Epirubicin is associated with dose-dependent cardiomyopathy, the incidence of which is related to cumulative dose. Assess baseline LVEF prior to initiating therapy. Epirubicin is contraindicated for patients with recent myocardial infarction, severe myocardial dysfunction (LVEF <50%), severe arrhythmias, or prior treatment with maximum cumulative doses of anthracyclines.
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
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Monitoring parameters: |
- Assess liver and kidney function tests prior to each treatment cycle.
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- Assess CBC with differential prior to and during each treatment cycle.
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- Monitor for diarrhea and cutaneous toxicity (palmar-plantar erythrodysesthesias).
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- Monitor cumulative epirubicin dose. Reassess LVEF periodically during FEC therapy as clinically indicated.
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Suggested dose modifications for toxicity: |
Myelotoxicity | - If the ANC is <1500/microL and platelets are <100,000/microL on day 1 of each cycle, therapy should be delayed until counts recover. For midcycle platelet count <40,000/microL and ANC <500/microL, reduce epirubicin by 10 mg/m2.[1]
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Gastrointestinal toxicity | - For ≥grade 2 mucositis (or other nonhematologic toxicity), reduce epirubicin by 10 mg/m2.[1] Withhold FU for grade 2 or worse diarrhea and restart at a lower dose after complete resolution.[3]
- NOTE: Severe diarrhea and mucositis after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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Cardiotoxicity | - In the original protocol, if cardiac symptoms developed or if during treatment the LVEF decreased by ≥10% in absolute value below the lowest normal limit, or ≥15% below the patient's own baseline, treatment was discontinued.[1]
- Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. There is no recommended dose for resumption of FU administration following development of cardiac toxicity, and the drug should be discontinued.[3]
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Palmar-plantar erythrodysesthesias | - Hold FU for grade 2 or greater palmar-plantar erythrodysesthesia, and reduce subsequent dose by 20%.[3]
- Refer to UpToDate topics on cutaneous complications of conventional chemotherapy agents.
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Neurologic toxicity | - There is no recommended dose for resumption of FU administration following development of hyperammonemic encephalopathy, acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances; the drug should be permanently discontinued.[3]
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If there is a change in body weight of at least 10%, doses should be recalculated. |