| Cycle length: 21 days. Duration of therapy: 6. |
| Drug | Dose and route | Administration | Given on days |
| Cycles 1 through 3 |
| Fluorouracil (FU) | 500 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 | 100 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 | 500 mg/m2 IV | Dilute with 250 mL NS or D5W* and administer over 30 to 60 minutes. | Day 1 |
| Cycles 4 through 6 |
| Docetaxel | 100 mg/m2 IV | Dilute in 250 mL NS or D5W* to a final concentration of 0.3 to 0.74 mg/mL and administer over 60 minutes. | Day 1 |
| 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.
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| Emesis risk | - The emesis risk with FEC is HIGH (>90% frequency of emesis).
- The emesis risk with docetaxel monotherapy is LOW (10 to 30% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Premedicate with dexamethasone prior to docetaxel administration.[3]
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Epirubicin is a vesicant; avoid extravasation.[4] Docetaxel is an irritant but can cause significant tissue damage; avoid extravasation.[3] FU and cyclophosphamide are irritants.
- 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 (incidence of neutropenic fever is 11%[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 renal dysfunction | - A lower starting dose of FU may be needed for patients with liver impairment, known DPD deficiency, or renal 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. Docetaxel should not be administered to patients with a serum bilirubin above the ULN or to patients with transaminase elevations >1.5 times the ULN in conjunction with alkaline phosphatase >2.5 times the ULN.[3].
- 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.
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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, 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.
|
| Dose adjustment for known drug interactions | - Caution is required if administering docetaxel with strong CYP3A4 inhibitors.¶ According to the United States Prescribing Information, avoid the use of docetaxel with strong CYP3A4 inhibitors (if possible). If concomitant therapy cannot be avoided, monitor closely for toxicity and consider a docetaxel dose reduction.[3] Docetaxel dose reductions for concomitant therapies should be individualized based on patient factors (eg, performance status) and the intent of therapy (ie, curative or palliative).
- Refer to "Suggested dose modifications for toxicity" below.
|
| Monitoring parameters: |
- Assess liver and renal function tests prior to each treatment cycle.
|
- Assess CBC with differential prior to and during each treatment cycle.
|
- Monitor for diarrhea and cutaneous toxicity (palmar-plantar erythrodysesthesias).
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- Assess changes in neurologic function prior to each treatment with docetaxel.
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- Monitor cumulative epirubicin dose. Reassess LVEF during therapy as clinically indicated.
|
- Patients with renal impairment, hyperuricemia, and bulky tumors are at risk for TLS and should undergo correction of dehydration and lowering of high serum uric acid levels prior to treatment initiation, and be closely monitored for TLS during and after treatment.
- Refer to UpToDate topics on tumor lysis syndrome.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - If ANC ≤1000/microL or platelets ≤100,000/microL on day 1 of each cycle, delay therapy until counts recover.[1] Dose reductions are suggested for ANC ≤500/microL for >5 days, ANC <100/microL for >3 days, a platelet count <25,000/microL, or febrile neutropenia. Reduce dose as follows upon recovery of counts to ≤grade 1: FU (375 mg/m2), epirubicin (75 mg/m2), cyclophosphamide (375 mg/m2), and docetaxel (75 mg/m2).[1]
|
| Gastrointestinal toxicity | - Grade 3 diarrhea or mucositis, reduce doses as follows upon recovery: FU (375 mg/m2), epirubicin (75 mg/m2), cyclophosphamide (375 mg/m2), and docetaxel (75 mg/m2).[1] For grade 4 diarrhea, hold treatment.[4]
- 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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| Palmar-plantar erythrodysesthesias | - Hold FU for grade 2 or greater palmar-plantar erythrodysesthesia, and reduce subsequent dose by 20%.[5]
- 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.[5]
|
| Cardiotoxicity | - 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]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
