Chapter 33: Hematologic Disorders

ANEMIA—USE OF ERYTHROPOIETIC AGENTS

Population

• –Adult patients with cancer and anemia.

Recommendation

American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO) 2010

• –Approach to anemic cancer patients

  • History, physical exam, and diagnostic studies to exclude other causes of anemia aside from chemotherapy or malignant marrow infiltration.

  • The FDA label now limits the use of Erythrocyte Stimulating Agents (ESA) ONLY to anemic cancer patients receiving chemotherapy with palliative intent. (N Engl J Med. 2007;356:2448) ESA is NOT to be used in patients with curable malignancies or in patients with cancer not on chemotherapy. Side effects of thrombosis and potentially increased cancer growth should be discussed with the patient. (J Natl Cancer Inst. 2013;105:1018)

  • Correct iron deficiency anemia: if iron saturation is <20% or ferritin <20, then PO/IV iron supplementation of elemental iron 40–195 mg per daily.

  • Epoetin and darbepoetin are equal in efficacy.

  • ESA should not be used if hemoglobin >10 g/dL. The main benefit of ESA is to reduce transfusion need. (Br J Cancer. 2010;102:301)

  • FDA-approved starting dose of epoetin is 150 U/kg 3 times/wk or 40,000 U weekly. For darbepoetin the dose is 2.25 µg/kg weekly or 500 µg every 3 wk subcutaneously.

  • Stop ESAs at 6–8 wk if no evidence of a response. Check for underlying tumor progression, iron deficiency, or other causes of anemia.

  • Dose of ESAs should be lowest concentration needed to avoid transfusion. Keep hemoglobin <12.

  • Periodic monitoring of ferritin and iron studies is recommended since ESAs will not improve hemoglobin if the patient is iron deficient.

  • Use of ESAs in lower-risk myelodysplastic syndrome to decrease transfusions is approved if erythropoietin level is <500 mµ/mL. The use of low-dose filgrastrin (100 μg once or twice/wk) will increase responsiveness to ESAs.

Sources

• –Aapro M, et al. Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(suppl 4):iv96–iv110.

• –ASH/ASCO guidelines update on use of epoetin and darbepoetin. Blood. 2010;116:4045-4059.

• –Schrier S, Steensma D, Loprinzi L. Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer. Uptodate.com. 2018.

Comments

1. Important facts about ESAs

   1. Early studies raising hemoglobin level to >12 g/dL resulted in significant increased risk of venous thromboembolus.

   2. Beware of clot risk when using ESAs with other thrombophilic drugs (tamoxifen, BCP, lenalidomide).

   3. The molecular structure of darbepoetin increases its half-life, allowing for less frequent injections.

   4. Fifty percent of cancers will have erythropoietin receptors on the cell surface. It has NOT been proven that ESAs’ interaction with cell surface receptors leads to cellular proliferation.

   5. When patients stop chemotherapy for any reason, ESAs must be stopped and transfusion therapy substituted according to FDA guidelines.

   6. The addition of intravenous iron to ESAs will increase hemoglobin more rapidly since iron is sequestered in the reticuloendothelial system in the cancer-associated anemia of chronic disease. (N Engl J Med. 2005;352:1011)

   7. ESAs are widely used in chronic renal insufficiency, reducing need for transfusion significantly. Iron is often given to these patients ...