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Chemotherapy-induced Anaemia
Sue Wilson (/authors/sue-wilson-0), Peter T Silberstein (/authors/peter-t-silberstein), Ibrahim T Aldoss
(/authors/ibrahim-t-aldoss)
Asia-Pacic Oncology & Haematology, 2008;1(1):24-6
Abstract:
Anaemia is a frequent complication of malignancy and is aggravated by chemotherapy
(http://www.touchoncology.com/articles/treatment-strategies-metastatic-renal-cell-carcinoma).1,2 Up to
90% of cancer patients experience anaemia during the course of the disease;1 however, the frequency
varies with the type and stage of the tumour and treatment. Chemotherapy reduces the haemoglobin
(Hgb) level by inducing a suppressive eect on bone marrow and toxic eects on erythrocytes. The
incidence of anaemia has been correlated directly with the number of chemotherapy cycles the patient
receives.3 Early studies demonstrated a profound adverse impact of anaemia on a cancer patients
functional capacity, quality of life (QOL), prognosis and survival.46 Pre-clinical studies have shown that
anaemia is associated with antineoplastic therapy resistance,7,8 which is partially attributed to the hypoxic
eect of anaemia and the reliance of ionising radiation, as well as certain types of chemotherapy agents,
on adequate tissue oxygenation for their ability to kill cancer cells. Therefore, anaemia theoretically
contributes to furthering malignant progression and tumour survival in the oncology anaemic patients.9
14

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Treatment of CIA
In malignant patients, it is crucial to consider potential reversible aetiologies of anaemia before starting
erythropoiesis-stimulating agents (ESAs). Therefore, a comprehensive history and physical examination are
warranted, and the exposure list of the medications should be reviewed. Screening diagnostic tests should be
conducted, which include iron studies, folate, vitamin B12 and peripheral blood smear. Patients should be
evaluated for occult blood loss and renal insuciency. In patients with underlying chronic lymphocytic
leukaemia and non-Hodgkins lymphoma, direct Coombs testing may be needed to exclude an autoimmune
mechanism of anaemia. Blood transfusion was the cornerstone therapy for many years in chemotherapyinduced anaemia (CIA), (http://www.touchoncology.com/articles/chemotherapy-induced-nausea-andvomiting) although this trend has changed because ESAs have decreased transfusion requirements. However,
transfusion remains the rst-line therapy if acute intervention is required and in patients who have failed or
have contraindications to ESAs. In addition, the change in US Food and Drug Administration (FDA) indication
does not allow ESAs to be given to CIA patients treated with curative intent.
The Introduction of ESAs and Their Ecacy in Reducing Transfusion Requirements
Three dierent recombinant erythropoietins (Epo) are available: epoetin alfa, pegzerepoetin alpha and
darbepoetin alpha. Pegzerepoetin alpha is not commercially available in the US. Darbepoetin alpha has an
additional Nlinked oligosaccharide chain that provides a three-fold greater terminal halife with a ve-fold
lower anity for Epo receptors compared with erythropoietin alfa.16 Trials and comprehensive systematic
reviews have shown equality of the dierent ESAs in Hgb rise and a reduction of transfusion requirements or
thromboembolic incidence;1721 therefore, the indications, concerns and warnings are similarly applied for all
ESAs. Epoetin alpha was approved by the FDA for treating CIA in patients with nonmyeloid malignancies in
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1993, followed by darbepoetin alpha in 2002. Trials have established their ecacy in raising Hgb levels and
reducing blood transfusion,2225 and a systematic review by Bohlius et al. has found that treatment with ESAs
increases Hgb levels and reduces the need for blood transfusions by 40%, with an average of one unit fewer
of red blood cells (RBCs) transfusion in patients receiving ESAs compared with the control group.24 The
advantage of ESAs over blood transfusion is their ability to induce a more sustained correction of Hgb,
remove the risk of blood-borne infectious agents and confer a more convenient therapy for the patient. The
use of ESAs has spread worldwide and has emerged as one of the most utilised medications in oncology,
despite the fact that studies have never proved a survival benet. The rationale behind their spread was the
belief of their ability to promote QOL.

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