DOSAGE AND ADMINISTRATION
ELLENCE Injection is administered to patients by intravenous infusion. ELLENCE is given in repeated 3- to 4-week cycles. The total dose of ELLENCE may be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle. The recommended dosages of ELLENCE are as follows:
STARTING DOSES
The recommended starting dose of ELLENCE is 100 to 120 mg/m2. The following regimens were used in the trials supporting use of ELLENCE as a component of adjuvant therapy in patients with axillary-node positive breast cancer:
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CEF-120:
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Cyclophosphamide
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75 mg/m2 PO D 1-14
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ELLENCE
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60 mg/m2 IV D 1, 8
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5-Fluorouracil
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500 mg/m2 IV D 1, 8
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Repeated every 28 days for 6 cycles
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FEC-100:
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5-Fluorouracil
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500 mg/m2 |
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ELLENCE
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100 mg/m2 |
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Cyclophosphamide
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500 mg/m2 |
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All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
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Patients administered the 120-mg/m2 regimen of ELLENCE also received prophylactic antibiotic therapy with trimethoprim-sulfamethoxazole (e.g., Septra® , Bactrim® ) or a fluoroquinolone.
Bone Marrow Dysfunction. Consideration should be given to administration of lower starting doses (75-90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration (see WARNINGS and PRECAUTIONS).
Hepatic Dysfunction. Definitive recommendations regarding use of ELLENCE in patients with hepatic dysfunction are not available because patients with hepatic abnormalities were excluded from participation in adjuvant trials of FEC-100/CEF-120 therapy. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions were recommended in clinical trials, although few patients experienced hepatic impairment:
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Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal
1/2 of recommended starting dose
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Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal
1/4 of recommended starting dose
Information regarding experience in patients with hepatic dysfunction is provided in CLINICAL PHARMACOLOGY, Pharmacokinetics In Special Populations.
Renal Dysfunction. While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, lower doses should be considered in patients with severe renal impairment (serum creatinine > 5 mg/dL).
DOSE MODIFICATIONS
Dosage adjustments after the first treatment cycle should be made based on hematologic and nonhematologic toxicities. Patients experiencing during treatment cycle nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity should have the Day 1 dose in subsequent cycles reduced to 75% of the Day 1 dose given in the current cycle. Day 1 chemotherapy in subsequent courses of treatment should be delayed until platelet counts are >/=100,000/mm3, ANC >/=1500/mm3, and nonhematologic toxicities have recovered to </= Grade 1.
For patients receiving a divided dose of ELLENCE (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000-100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grade 3/4 nonhematologic toxicity has occurred, the Day 8 dose should be omitted.
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