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:
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:
|CEF-120: ||Cyclophosphamide |
Repeated every 28 days for 6 cycles
|75 mg/m2 PO D 114 |
60 mg/m2 IV D 1, 8
500 mg/m2 IV D 1, 8
|500 mg/m2 |
| || |
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
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 (7590 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).
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:
- Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose
- 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.
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).
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 75,000100,000/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.
Preparation & Administration Precautions
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures normally used for proper handling and disposal of anticancer drugs should be considered for use with ELLENCE. Several guidelines on this subject have been published.18
The following protective measures should be taken when handling ELLENCE:
- Personnel should be trained in appropriate techniques for reconstitution and handling.
- Pregnant staff should be excluded from working with this drug.
- Personnel handling ELLENCE should wear protective clothing: goggles, gowns and disposable gloves and masks.
- A designated area should be defined for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper.
- All items used for reconstitution, administration or cleaning (including gloves) should be placed in high-risk, waste-disposal bags for high temperature incineration.
- Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All contaminated and cleaning materials should be placed in high-risk, waste-disposal bags for incineration. Accidental contact with the skin or eyes should be treated immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Medical attention should be sought. Always wash hands after removing gloves.
Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug. ELLENCE should not be mixed with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
ELLENCE can be used in combination with other antitumor agents, but it is not recommended that it be mixed with other drugs in the same syringe.
Preparation of Infusion Solution
ELLENCE is provided as a preservative-free, ready-to-use solution.
ELLENCE should be administered into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100120 mg/m2 should generally have epirubicin infused over 1520 minutes. For patients who require lower epirubicin starting doses due to organ dysfunction or who require modification of epirubicin doses during therapy, the epirubicin infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein (see PRECAUTIONS). ELLENCE should be used within 24 hours of first penetration of the rubber stopper. Discard any unused solution.