Radiation Oncology/Anemia


 * ASCO and NCCN recommend maintaining Hb near 12 g/dL. Should initiate therapy when Hb drops to 11 or lower.
 * However, randomized data from H&N, breast, and NSCLC show adverse outcomes in patients undergoing therapy with Epo support
 * H&N Epo data
 * Breast Epo data
 * NSCLC Epo data
 * A general randomized trial enrolling patients with Hb <11 showed no improved in transfusion requirements, and significantly worse survival with darbepoetin alfa

Darbepoetin Alfa (Aranesp)

 * FDA recommended doses
 * Starting dose: 2.25 mcg/kg SC injection qweek
 * May increase to 4.5 mcg/kg if less than 1g/dL increase in Hb over 2 weeks
 * Other doses
 * 3 mcg/kg q2week
 * 200 mcg q2week
 * 300 mcg q3week


 * Multi-National (Europe, North America, Australia)(2004-2006)
 * Randomized. 989 patients. Non-myeloid malignancies (NSCL 18%, breast 13%), anemia Hgb <11 (mean 9.5), not receiving chemo or RT. Arm 1) placebo vs. Arm 2) darbepoetin alfa 6.75 ug/kg q4w x 16 weeks
 * 2008 PMID 18227526 -- "Darbepoetin Alfa for the Treatment of Anemia in Patients With Active Cancer Not Receiving Chemotherapy or Radiotherapy: Results of a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study." (Smith RE Jr, J Clin Oncol. 2008 Jan 28 [Epub ahead of print])
 * Outcome: Transfusions week 5-17 similar. Median OS DA 8.5 months vs. placebo 10.8 months (SS)
 * Toxicity: more cardiovascular, thromboembolic events, more deaths
 * Conclusion: Darbepoetin no impact on transfusions, worse survival

IV Iron

 * Italy (2004-2006) -- darbepoetin +/- IV iron
 * 2008 PMID 18375891 -- "Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha." (Pedrazzoli P, J Clin Oncol. 2008 Apr 1;26(10):1619-25.)
 * Randomized. 149 patients with lung, GYN, BCA, and CRC; Hb <=11 g/L and no iron deficiency. Treated with darbepoetin and Arm 1) control vs. Arm 2) IV iron (sodium ferric gluconate) 125mg IV Q1W x6 weeks
 * Outcome: Hb response EPO 62% vs. EPO + Iron 77% (SS)
 * Toxicity: Comparable
 * Conclusion: IV supplementation reduces treatment failures to darbepoetin


 * European Multi-Institutional -- darbepoetin +/- IV iron
 * Randomized. 396 patients with non-myeloid malignancies, Hb <11 g/dL. Treated with darboepoetin and Arm 1) control vs. Arm 2) IV iron Q3W x 4 months
 * 2008 PMID 18375890 -- "Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia." (Bastit L, J Clin Oncol. 2008 Apr 1;26(10):1611-8.)
 * Outcome: % achieving Hb >=12 EPO 73% vs. EPO + Iron 86% (SS); also fewer transfusions 20% vs. 9% (SS)
 * Toxicity: No difference in adverse events; iron-related were GI
 * Conclusion: Addition of IV iron to darbepoetin improved Hb control and decreased number of transfusions


 * Sundsvall (2003-2005) -- EPO +/- IV iron
 * Randomized. 67 patients, lymphoproliferative malignancy, Hb 9-11 g/dL. Treated with epoetin 30,000 IU Q1W and Arm 1) control vs. Arm 2) IV iron 100 mg QW
 * 2007 PMID 17252006 -- "Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study." (Hedenus M, Leukemia. 2007 Apr;21(4):627-32. Epub 2007 Jan 25.)
 * Outcome: Hb response EPO 53% vs. EPO + IV iron 93%; mean weekly EPO dose lower >25% in IV iron group by week 15 (p=0.05)
 * Conclusion: Hb reponse significantly improved with IV iron


 * Karnell Cancer Center -- epoetin +/- oral iron or IV iron
 * 2007 PMID 17296819 -- "Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy." (Henry DH, Oncologist. 2007 Feb;12(2):231-42.)
 * Randomized. 129 patients, Hb <11 g/d, ferritin >= 100 ng/ml, transferring >=15%. Treated with epoetin 40,000 U and Arm 1) control vs. Arm 2)oral ferrous sulfacte 325 mg TID vs. Arm 3) IV ferric gluconate 125 mg IV Q1W
 * Outcome: Hb response EPO 41% vs. EPO + oral iron 46% vs. EPO + IV iron 73% (SS)
 * Toxicity: Well tolerated
 * Conclusion: IV iron in addition to epoetin produces significantly greater Hb response


 * Averbach Hematology-Oncology -- rHuEPO +/- oral iron or IV iron
 * Randomized. 157 patients, Hb <=10.5 g/dL or ferritin <=450 pmol/L or transferring <=19%. Treated with rHuEPO 40,000 U QW and Arm 1) control vs. Arm 2) oral iron 325 mg BID vs. Arm 3) IV iron (iron dextran) 100 mg bolus vs. Arm 4) IV iron (iron dextran) 100 mg infusion
 * 2004 PMID 15051778 -- "Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial." (Auerbach M, J Clin Oncol. 2004 Apr 1;22(7):1301-7.)
 * Outcome: Hematopoietic response EPO 25% vs. EPO + oral iron 36% vs. EPO + IV iron 68% (both groups). IV iron groups had improved energy, activity and QoL, oral iron group no difference, and no iron worsening
 * Conclusion: IV iron improves effect of EPO