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ISSN 1527-3172 (Electronic)

2010, Number 3

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MEDICC Review 2010; 12 (3)

Efficacy and safety of ior®EPOCIM for chemotherapy-or radiotherapy-induced anemia in pediatric cancer patients

Vargas A, Mendoza I, Uranga R, González A, Martínez L, Caballero I, Piedra P, Saurez G, Verdecia M, Cabanas R

Language: English
References: 37
Page: 27-31
PDF size: 64.19 Kb.


ABSTRACT

Introduction: Recombinant human erythropoietin (RHuEPO) is an erythropoiesis stimulating agent (ESA) used to treat anemia in patients with total or relative erythropoietin deficit. In cancer patients, it is administered to optimize hemoglobin (Hb) levels, correct anemia and reduce the need for transfusions. Cuba produces a RHuEPO, registered in 1998 as ior®EPOCIM, that is widely used in the national public health system, mainly to treat patients with anemia due to chronic kidney disease (CKD).
Objective: Evaluate the efficacy and safety of iorr®EPOCIM in pediatric cancer patients with anemia following chemotherapy or radiotherapy. The working hypothesis posed an Hb increase ≥ 15 g/l in 70% of patients receiving iorr®EPOCIM for 8 weeks.
Methods: A Phase IV, multicenter, open clinical trial was conducted. Participants were 157 patients aged 1–19 years with anemia and cyto-histological diagnosis of cancer in any location. Patients received either 600 U/kg iorr®EPOCIM intravenously, once weekly, or 150 U/kg iorr®EPOCIM subcutaneously, 3 times a week, for 8 weeks. All patients had blood tests every week to determine hemoglobin and hematocrit, and reticulocyte and platelet counts. Mean number of transfusions required by patients during the treatment period was compared to the mean number of transfusions received in the preceding 8 weeks. Adverse events (AE) were recorded at the 4th and 8th weeks and classifi ed by intensity and causality.
Results: Hb levels rose ≥ 15 g/l in 68.8% of patients, and transfusion requirements decreased 17%. The most frequent adverse events were fever (19.3%), vomiting (10.2%) and flu-like syndrome (9.6%). Intensity of AE was predominantly mild. Only 7 AE were classified as very probably related to the product and none of those was severe.
Conclusions: ior®EPOCIM proved to be safe and effective at the doses and frequencies used in this patient population. As a result, this medication was recommended for use in all pediatric oncology and hematology services in the country.


REFERENCES

  1. Silvia M, Grillot D, Benito A, Richard C, Nuñez G, Fernández-Luna JL. Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2. Blood. 1996 Sep 1;88(5):1576–82.

  2. Huraib S, Abu-Aisha H, al-Momen A, al- Wakeel J, Memon N, al-Tuwaijri A. Effect of recombinant human erythropoietin on lymphocyte phenotyping and phagocyte activity in hemodialysis patients. Am J Kidney Dis. 1997;29:866–70.

  3. Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC, et al. Cloning and expression of the human erythropoietin gene. Proc Nat Acad Sci USA.1985;92:7850–84.

  4. Andrade L. Agentes estimulantes de la eritropoyesis. Rev Nefrol Diálisis Traspl. 2008 Jun;28(2):73–82.

  5. Marsden JT. Erythropoietin – measurement and clinical applications. Ann Clin Biochem. 2006;43:97–104.

  6. Eschbach JW, Abdulhadi MH, Brownie JK, Delano BG, Downing MR, Egrie JC, et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial. Ann Intern Med. 1989 Dec 15;111(12):992–1000.

  7. Ifudu O, Feldman J, Friedman EA. The Intensity of Hemodialysis and the Response to Erythropoietin in Patients with End-Stage Renal Disease. N Engl J Med. 1996 Feb 15;334:420–5.

  8. Singh A, Szczech L, Tang K, Barnhart H, Sapp S, Wolfson M, et al. Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease. N Engl J Med. 2006;355:2085–98.

  9. Lappin T, Maxwell AP, Johnston PG. Warning Flags for Erythropoiesis-Stimulating Agents and Cancer- Associated Anemia. Oncologist. 2007;12:362–5.

  10. Ng T, Marx G, Littlewood T, Macdougall I. Recombinant erythropoietin in clinical practice. Postgrad Med J. 2003;79:367–76.

  11. Registro Sanitario de Medicamentos y Biológicos aprobados. Centro para el Control Estatal de la Calidad de los Medicamentos [Internet]. Havana: Ministry of Public Health (CU); [updated 2010; cited 2010 Jun 21]. Available from: www. cecmed. sld.cu/Docs/RegSan/RegSanMed.xls

  12. Pérez-Oliva JF, Morejón B, Vargas A, Lagarde M, Mendoza I, Viada CE. Equivalencia terapéutica entre ior®EPOCIM y EPO sin albúmina en pacientes con insufi ciencia renal crónica en hemodiálisis. Rev Haban Cienc Méd. 2008 Jul–Sep;7(3).

  13. Pérez JF, Casanova M, García I, Porrero PJ, Valenzuela C, Hernández T, et al. Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: a parallel, randomized double blind study. BMC Nephrology. 2005;6:5.

  14. Estrin JT, Schocket L, Kregenow R, Henry DH. A Retrospective Review of Blood Transfusions in Cancer Patients with Anemia. Oncologist. 1999 Aug;4(4):318–24.

  15. Caro JJ, Salas M, Ward A. Anemia as an independent prognostic factor for suvirval in patients with cancer. Cancer. 2001;91:2214–21.

  16. Gordon MS. Managing anemia in the cancer patient: old problems, future solutions. Oncologist. 2002;7:331–41.

  17. Rizzo JD, Somerfi eld MR, Hagerty KL, Seidenfel J, Bohlius J, Bennett CL, et al. Use of Epoetin and Darbepoetin in Patients with Cancer: 2007 American Society of Clinical Oncology /American Society of Hematology Clinical Practice Guideline Update. J Clin Oncol. 2008;26:132–49.

  18. Marec-Berard P, Chastagner P, Kassab-Chahmi D, Casadevall N, Marchal C, Misset JL, et al. 2007 Standards, Options, and Recommendations: Use of Erythropoiesis-Stimulating Agents (ESA: Epoetin Alfa, Epoetin Beta, and Darbepoetin) for the Management of Anemia in Children With Cancer. Pediatr Blood Cancer. 2009 Jul;53(1):7–12.

  19. Case DC Jr, Bukowski RM, Carey RW, Fishkin EH, Henry DH, Jacobson RJ, et al. Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. J Natl Cancer Inst. 1993 May 19;85(10):801–6.

  20. Henry DH, Brooks BJ Jr, Case DC Jr, Fishkin E, Jacobson R, Keller AM, et al. Recombinant human erythropoietin therapy for anemic cancer patients receiving cisplatin chemotherapy. Cancer J Sci Am. 1995 Nov–Dec;1(4):252–60.

  21. Varan A, Büyükpamukçu M, Kutluk T, Akyüz C. Recombinant human erythropoietin treatment for chemotherapy-related anemia in children. Pediatrics. 1999 Feb;103(2):E16.

  22. Porter J. Erythropoietin use in Pediatric Oncology. Transfusion Alternatives in Transfusion Medicine. 2002 Feb;4(1):20–5.

  23. León P, Jiménez M, Barona P, Sierrasesúmaga L. Recombinant human erythropoietin for the treatment of anemia in children with solid malignant tumors. Med Pediatr Oncol. 1998 Feb;30(2):110–6.

  24. Bolonaki I, Stiakaki E, Lydaki E, Dimitriou H, Kambourakis A, Kalmantis T, et al. Treatment with recombinant human erythropoietin in children with malignancies. Pediatr Hematol Oncol. 1996;13:111–21.

  25. Informe Final del Ensayo Clínico: Impacto del ior EPOCIM en pacientes oncológicos portadores de anemia post-quimioterapia o radioterapia. Havana: CIMAB; 2008.

  26. Glader B. Nelson Tratado de Pediatría. 17th ed. Madrid: Elsevier; c2004. Las Anemias; p.1604–6.

  27. Declaración de Helsinki de la Asociación Médica Mundial. Principios éticos para las investigaciones médicas en seres humanos [Internet]. Helsinki; 1964 [updated 2004 Oct 9; cited 2010 May 26]; [about 15 screens]. Available from: http://www.saber.ula.ve/bitstream/1234567 89/16099/1/declaracion_helsinski.pdf

  28. Council for International Organizations of Medical Sciences. Pautas Éticas Internacionales para la Investigación Biomédica en Seres Humanos. [Internet]. Geneva; 2002 [cited 2010 May 26]; [about 150 screens]. Available from: http://www. cioms.ch/publications/guidelines/pautas_eticas_ internacionales.htm

  29. Procedimientos Normalizados de Trabajo. Havana: Centro Nacional Coordinador de Ensayos Clínicos (CU); 2004.

  30. Jones JK. Adverse drug reactions in the community health setting; approaches to recognizing, counseling and reporting. Fam Community Health. 1982;5(2):58–67.

  31. Razzouk BI, Hord JD, Hockenberry M, Hinds PS, Feusner J, Williams D, et al. Double-Blind, Placebo-Controlled Study of Quality of Life, Hematologic End Points, and Safety of Weekly Epoetin Alfa in Children With Cancer Receiving Myelosuppressive Chemotherapy. J Clin Oncol. 2006 Aug;24(22):3583–9.

  32. Abdelrazik N, Fouda M. Once weekly recombinant human erythropoietin treatment for cancer-induced anemia in children with acute lymphoblastic leukemia receiving maintenance chemotherapy: a randomized case-controlled study. Hematology. 2007 Dec;12(6):533–41.

  33. Bennetts G, Bertolone S, Bray G. Erythropoietin reduces volume of red cell transfusions required in some subsets of children with acute lymphocytic leukaemia. Blood. 1995;10:853.

  34. Ramos EJ, Suzuki S, Marks D, Inui A, Asakawa A, Meguid MM. Cancer anorexia-cachexia syndrome: cytokines and neuropeptides. Curr Opin Clin Nutr Metab Care. 2004 Jul;7(4):427–34.

  35. Global Dysregulation: The Foundation of Involuntary Weight Loss in Cancer Patients. J Support Oncol. 2006 Feb;4(2):89–90.

  36. Muirhead N, Churchill DN, Goldstein M, Nadier SP, Posen G, Wong C, et al. Comparison of Subcutaneous and Intravenous Recombinant Human Erythropoietin for Anemia in Hemodialysis Patients with Signifi cant Comorbid Disease. Am J Nefrol. 1992;12(5):303–10.

  37. Jensen JD, Madsen JK, Jensen LW. Comparison of dose requirement, serum erythropoietin and blood pressure following intravenous and subcutaneous erythropoietin treatment of dialysis patients IV and SC erythropoietin. Eur J Clin Pharmacol. 1996;50(3):171–7.




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