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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Changing Paradigms in Anemia Management


GOAL
To provide physicians with current information and recommendations regarding the management of anemia in patients with cancer.

TARGET AUDIENCE
This activity is designed for hematologists and oncologists.

LEARNING OBJECTIVES
After reading this issue, the participant should be able to:

  • Understand the ramifications of chemotherapy-induced anemia on quality of life and mortality.
  • Explain the hematological factors that form the basis of erythropoiesis.
  • Describe and evaluate the effectiveness of a particular management strategy in an anemic patient undergoing chemotherapy.
  • Explain the implications of new clinical data related to dosing and efficacy of standard drug therapy.

ACCREDITATION STATEMENT
This activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education. The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education (CME) for physicians. The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1 hour in Category 1 credit toward the American Medical Association Physicians' Recognition Award. Each physician should claim only those hours of credit that he/she actually spends on this educational activity. Credits are available until the expiration date of October 31, 2004.

This continuing education activity was produced under the supervision of Jerry L. Spivak, MD, Professor of Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

This program is supported by an unrestricted educational grant from Amgen, Inc.

Publisher's Note and Disclaimer: The opinions expressed in this issue are those of the authors, presenters, and/or panelists and are not attributable to the publisher, editor, advisory board of Advanced Studies in Medicine, or The Johns Hopkins University School of Medicine or its Office of Continuing Medical Education. Clinical judgment must guide each professional in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this issue are not necessarily the same as indicated in the package insert for the product and may reflect the clinical experience of the authors, presenters, and/or panelists or may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, LLC, an HMG Company. P.O. Box 340, Somerville, NJ 08876. (908) 253-9001. Web site: www.galenpublishing.com. Copyright ©2001 by Galen Publishing, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Bulk postage paid at Somerville, NJ Post Office and at additional mailing offices. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC. Printed on acid-free paper. BPA Membership applied for December 2000.

The contents of this issue of Advanced Studies in Medicine include a review article, a case study, and highlights from the 38th Annual Meeting of the American Society of Clinical Oncology held in Orlando, Florida, May 18-21, 2002.

FACULTY ADVISOR

    Jerry L. Spivak, MD
    Professor of Medicine
    Division of Hematology
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Spivak reports serving as a consultant for Amgen, Inc, Ortho Biotech, and Novartis; and holding stock in Amgen, Inc.

PARTICIPATING FACULTY

    Stephen J. Noga, MD, PhD
    Director, Hematology/Medical Oncology
    Director, Bone Marrow Transplant and Cellular Therapeutics Program
    Alvin and Lois Lapidus Cancer Institute
    Sinai Hospital of Baltimore
    Baltimore, Maryland
    • Dr Noga reports serving as a consultant for Amgen, Inc; and receiving honoraria from Amgen, Inc. Advanced Studies in Medicine makes every effort to provide the reader with full disclosure information from major contributors. Advanced Studies in Medicine does not provide disclosure information for authors of poster presentations. The reader shall be advised that authors and coauthors on poster presentations may or may not maintain financial or advisory relationships with pharmaceutical companies.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Changing Paradigms in Anemia Management
Jerry L. Spivak, MD*

Anemia is a common complication of cancer, affecting one third to one half of patients. Although the causes of cancer-related anemia are diverse, impaired erythropoietin production and impaired responsiveness of erythroid progenitor cells to the hormone are central to its pathophysiology. Therefore, alleviating the anemia of cancer requires an understanding of how erythropoietin stimulates red blood cell formation, and how cancer alters the production of and response to this glycoprotein hormone.

The consequences of cancer-related anemia are as diverse as its causes, but all contribute to a reduction in the patient's quality of life. Of the many symptoms of anemia, fatigue has the most profound negative impact on the patient's ability to participate in everyday activities. Fortunately, anemia can now be corrected with recombinant human erythropoietin and its newer analogs. Data from randomized placebo-controlled trials and community-based observational studies indicate that correcting cancer-related anemia by stimulating erythropoiesis improves overall quality of life as well as physical activity, energy level, and psychosocial well-being.

The introduction of less frequent dosing schedules has further improved the treatment of cancer-related anemia. Darbepoetin alfa, a long-acting analog of recombinant erythropoietin, may offer even more dosing options by reducing the frequency of injection to once every few weeks. These changes represent major improvements in patient convenience. Future studies should further define the most efficient means of exploiting these important biologic agents.

This issue of Advanced Studies in Medicine includes a review of cancer-related anemia and erythropoiesis, which discusses the basis of erythropoiesis and how it is impaired in cancer-related anemia, as well as recent scientific advances for improving the treatment of anemia.

Dr Stephen Noga's case study demonstrates that tumor involvement of the bone marrow can produce anemia severe enough to provoke myocardial ischemia. His case study also highlights the importance of evaluating a patient's iron body stores before initiating erythropoietin therapy and the effectiveness of front-loading with weekly dosing of darbepoetin alfa, followed by less frequent maintenance dosing.

Several poster presentations from the 2002 annual meeting of the American Society of Clinical Oncology are also covered in this issue. Ludwig et al reported on the European Cancer Anaemia Survey, which collected data from more than 15 000 patients with cancer who were undergoing various forms of treatment in oncology practices throughout Europe. The researchers' goal was to create a comprehensive prospective database large enough to enable documentation of the prevalence, incidence, severity, evolution, associated factors, and management of cancer-related anemia. The data showed that cancer-related anemia was common and undertreated. Despite the negative effects of even mild-to-moderate anemia on a patient's performance status, treatment is not often initiated until hemoglobin levels are severely low and could compromise the patient's daily functioning, physical health, and quality of life.

In the study by Jacobsen et al, patients completed questionnaires assessing their level of fatigue and cognitive difficulties before beginning chemotherapy. In addition, a psychometrist evaluated the patient's attention level, cognitive function, and visual memory. The tests were repeated after the third cycle of chemotherapy. The researchers found that declining hemoglobin levels could reduce cognitive abilities, in addition to previously reported negative effects on fatigue and quality of life.

A randomized active-controlled study by Glaspy et al evaluated whether a faster erythropoietic response could be safely achieved by using a regimen that combined front-loaded weekly dosing of darbepoetin alfa, followed by lower, less frequent maintenance dosing in patients with solid tumors who were undergoing multicycle chemotherapy. The researchers found that delivering darbepoetin alfa in doses of 4.5 mcg/kg per week for 4 weeks, followed by 3.0 mcg/kg every 2 weeks, achieved a more rapid and sustained hemoglobin response and relief from fatigue compared with weekly epoetin alfa therapy. The use of a front-loading dosing strategy also appeared to be well tolerated.

As part of the same study, Kallich et al investigated the effects on quality of life of delivering darbepoetin alfa in regimens designed to achieve a more rapid correction of anemia. The researchers found that patients who received loading doses of darbepoetin alfa had greater and faster improvements in several aspects of their quality of life, including fatigue, physical and functional well-being, and overall health. Additional benefits appeared to include a reduction in caregiver burden during chemotherapy.

This monograph provides a framework for understanding the causes, consequences, and treatment of cancer-related anemia. It also emphasizes the need for future research to further define the circumstances under which erythropoietin therapy is indicated and the most efficient way to deliver recombinant erythropoietin and its newer analogs.

*Professor of Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, Maryland.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.