Cycle length: 21 days (FEC), 7 days (paclitaxel).
Duration of therapy: 12 weeks (FEC), 8 weeks (paclitaxel). |
| Drug | Dose and route | Administration | Given on days |
| Cycles 1 through 4 |
| Fluorouracil (FU) | 600 mg/m2 IV | Drug is available in 50 mg/mL solution that needs no further dilution prior to administration as slow IV push over five minutes. | Day 1 |
| Epirubicin | 90 mg/m2 IV | Administer as an IV push into a free-flowing IV solution with NS or D5W*, generally over 3 to 20 minutes. May dilute in NS or D5W* and infuse over 30 to 60 minutes. | Day 1 |
| Cyclophosphamide | 600 mg/m2 IV | Dilute with 250 mL NS or D5W* and administer over 30 to 60 minutes. | Day 1 |
| Cycles 5 through 12 |
| Paclitaxel | 100 mg/m2 IV | Dilute in 250 mL NS* and administer over one hour; special tubing needed.¶ | Weekly for 8 weeks |
| Pretreatment considerations: |
| Hydration | - Patients receiving cyclophosphamide should maintain adequate oral hydration (2 to 3 L/day during administration and for one to two days after) and void frequently to reduce the risk of hemorrhagic cystitis.[2]
- Refer to UpToDate topics on hemorrhagic cystitis in cancer patients.
|
| Emesis risk | - The emesis risk with FEC is HIGH (>90% frequency of emesis).
- The emesis risk with paclitaxel monotherapy is LOW (10 to 30% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Premedicate with dexamethasone plus both an H1 and an H2 receptor antagonist prior to paclitaxel administration.[3]
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Vesicant/irritant properties | - Epirubicin is a vesicant; avoid extravasation.[4] Paclitaxel can cause significant tissue damage; avoid extravasation.[3] Fluorouracil and cyclophosphamide are irritants.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| 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.
|
| Dose adjustment for baseline liver or renal dysfunction | - A lower starting dose of paclitaxel may be needed in patients with liver impairment. 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 renal impairment. A lower starting dose of epirubicin may be needed in patients with renal or hepatic impairment.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal 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.
|
| 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, 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.
|
| Monitoring parameters: |
- Assess liver and renal function tests prior to each treatment.
|
- Assess CBC with differential prior to and during each treatment.
|
- Monitor for diarrhea and cutaneous toxicity (palmar-plantar erythrodysesthesias).
|
- Assess changes in neurologic function prior to each treatment with paclitaxel.
|
- Monitor cumulative epirubicin dose. Reassess LVEF periodically during therapy as clinically indicated.
|
| Suggested dose modifications for toxicity:Δ |
| Myelotoxicity | - If the ANC ≤1500/microL or platelets ≤75,000/microL on day 1 of each cycle, therapy should be delayed until counts recover. For grade 3 clinically relevant toxicity during treatment, reduce doses of all drugs by 25%.[1]
|
| Gastrointestinal toxicity | - Hold FU for grade 3 diarrhea or mucositis until recovery to ≤grade 1. Upon recovery, reduce FU dose by 25%.[1] Discontinue therapy for grade 4 gastrointestinal (or other nonhematologic) toxicity.[1]
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| Neurotoxicity | - For grade 2 or higher peripheral neuropathy, reduce paclitaxel doses by 20%.[3]
- 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.[5]
|
| Cardiotoxicity | - Discontinue therapy for any clinically significant adverse cardiac events.[1]
- Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, ECG changes, and cardiomyopathy. There is no recommended dose for resumption of FU administration following development of cardiac toxicity, and the drug should be discontinued.[5]
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
