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Regimen: Darbepoetin Alfa (ARANESP®)
In adult patients with metastatic, nonmyeloid malignancies receiving myelosuppressive chemotherapy:
Therapy should not be initiated if Hgb is ≥10 g/dL
ESA treatment should target the lowest Hgb level that will avoid RBC transfusion
ESA therapy is not indicated for patients receiving chemotherapy with curative intent
Patients with cancer who are receiving myelosuppressive chemotherapy:
Darbepoetin 2.25 mcg/kg; administer by subcutaneous injection, once weekly, or
Darbepoetin alfa 500 mcg; administer by subcutaneous injection, once every 3 weeks
NCCN guidelines list alternative dosing schedules for consideration:
Darbepoetin 100 mcg weekly
Darbepoetin 200 mcg biweekly
Darbepoetin 300 mcg every three weeks
Notes:
NCCN Guidelines® include alternative fixed dose schedules for consideration:2
Darbepoetin alfa 100 mcg; administer by subcutaneous injection, once weekly, or
Darbepoetin alfa 200 mcg; administer by subcutaneous injection, once every 2 weeks, or
Darbepoetin alfa 300 mcg; administer by subcutaneous injection, once every 3 weeks
For patients who receive weekly darbepoetin, if Hgb increases <1 g/dL and remains <10 g/dL after 6 weeks of therapy, increase the darbepoetin dosage to 4.5 mcg/kg per week
If Hgb increases >1 g/dL in a 2-week period or Hgb reaches a level needed to avoid transfusion, reduce the dosage by 40% of dose previously administered
If Hgb exceeds a level needed to avoid transfusion, hold therapy until Hgb approaches a level where transfusion may be required, then reinitiate at a dosage decreased by 40% from the dose previously administered
Discontinue darbepoetin following completion of a chemotherapy course, or, if after 8 weeks of therapy there is no response as measured by Hgb levels or if transfusions are still required
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Therapy Monitoring4
Until a maintenance dose established and after any dose adjustment: Monitor Hgb weekly until hemoglobin is stable and sufficient to minimize the need for RBC transfusion
After Hgb stabilized: Monitor Hgb at regular intervals
Monitor iron, folate, and vitamin B12 status before and during treatment. Supplementation is recommended if serum ferritin <100 mcg/L or serum transferrin saturation <20%, or folate or vitamin B12 are less than the range of normal concentrations
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Indications4
Patients with neoplastic diseases
Anemia from concomitantly administered chemotherapy that is expected to continue for a minimum of 2 months (non-curative intent) in patients with metastatic, nonmyeloid malignancies
Patients with non-neoplastic diseases
Anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis
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Efficacy
Darbepoetin once weekly dosing was studied in advanced lung cancer patients (both SCLC and NSCLC) with Hgb values <11g/dL who were receiving platinum containing chemotherapy regimens. At 12 weeks, a significantly lower proportion of patients who received darbepoetin vs. placebo required a RBC transfusion (26% vs. 50%, respectively)4
Efficacy of darbepoetin 500 mcg administered once every 3 weeks versus 2.25 mcg/kg weekly was studied in patients with a Hgb <11g/dL undergoing cytotoxic chemotherapy. Seventy-two percent of patients required dose reductions in the every-3-weeks group whereas 77% required dose reductions in the once weekly group. Twenty-three percent of patients in the once-every-3-weeks group required RBC transfusion and 28% of the weekly group required RBC transfusion4,10
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The Epogen®/Procrit® and Aranesp® revised package inserts include two additional documents: a “Medication Guide” and “A Patient Instructions for Use.” The Medication Guide provides patients with important information necessary for safe and effective use of Epogen®/Procrit® and Aranesp®. Under FDA regulations, a Medication Guide must be distributed to all patients to whom the products are dispensed2
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Prescribers should discuss with their patients the benefits of treatment with ESAs and the potential and demonstrated risks of ESAs for thrombovascular events (myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access), increased risk of tumor progression or recurrence, and shortened survival time of cancer patients before starting or continuing therapy with ESAs
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In the United States, the Centers for Medicare and Medicaid Services (CMS) has ruled that Medicare will not underwrite the cost of ESAs for patients whose Hgb concentration is >10 g/dL, as stated in the July 2007 National Coverage Determination on ESAs. Currently, CMS does not make a distinction in ESA coverage between curative and palliative goals11
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In June 2008, the European Medicines Agency recommended that the ESAs prescribing information state that “blood transfusion should be the preferred method of correcting anemia in patients suffering cancer”12
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