Is Erythropoietin an Effective Treatment Option for Patients with Chemotherapy-Associated Anemia - Essay Example

Studies conducted amongst patients with malignancies have revealed that malignancy induces an inflammatory state in the body, leading to depressed production of erythropoietin.  Anemia related to treatment, both chemotherapy, and radiotherapy, can occur either due to myelotoxicity, i.e. damage to the erythroid precursors in the bone marrow, or myelosupression (Bokemeyer, et al., 2004, p. 2201). Until the advent of erythropoietic agents, such as Erythropoietin, Allogeneic red blood cell (RBC) transfusions were the mainstay of therapy for chemotherapy-associated anemia. However, transfusions are associated with certain risks and also have the limitation of being just a temporary measure for the amelioration of anemia (Bokemeyer, et al., 2004, p. 2202) and thus are used cautiously and have limited use in clinical practice nowadays.

This evidence-based review aims to elucidate the effectiveness of Erythropoietin as a treatment option for patients suffering from anemia that has occurred as a consequence of chemotherapy. The data for this literature review will be obtained via a comprehensive literature search conducted via various databases. The studies included in this review will be selected if they meet certain preset inclusion criteria and meet the required assessment criteria for reliability and validity. Moreover, this EBR also aims to formulate a set of recommendations regarding the indications, optimal dosing, and duration of therapy of erythropoietin use for the treatment of chemotherapy-related anemia in cancer patients which will serve as an update to the currently existing recommendations for erythropoietin use.

The objective of the Review:

Primary Question:

Is Erythropoietin an effective treatment option for adult patients with chemotherapy-associated anemia? 

Secondary Questions:

At what level of Hemoglobin is the use of Erythropoietin warranted and beneficial and is there a cut-off level of hemoglobin to initiate Erythropoietin therapy?

What are the optimal route, dosage, and duration of treatment for erythropoietin therapy?

Definitions:

• Subjects: Individuals with malignancies (both solid tumors and hematological malignancies)
• Intervention: Erythropoietin
• Outcomes: Need for transfusions and Quality of Life (QoL) measurements such as Functional Assessment of Cancer Therapy-Fatigue score
• Designs: Both randomized and nonrandomized but controlled trials of patients treated for Chemotherapy Induced Anemia (CIA)
• Comparators: RBC Transfusions

Subjects

Intervention

Outcomes

Comparators

Designs

Individuals with malignancies (both solid tumors and hematological malignancies)

Erythropoietin

Need for transfusions and Quality of Life (QoL) measurements such as Functional Assessment of Cancer Therapy-Fatigue score

RBC transfusions

Both randomized and nonrandomized but controlled trials of patients treated for Chemotherapy Induced Anemia (CIA)

Table 1: Definition of components of the primary systematic review question

 Methods:

A comprehensive computerized literature search was carried out. The following databases were used to search for all articles published during the last twenty years, i.e. from 1990 till 2010:

• PUBMED
• MEDLINE
• Cochrane Library
• CANCERLIT
• EBSCO
• EMBASE

Moreover, abstracts and publications from important meetings and conferences such as the American Society of Clinical Oncology (ASCO), American Society of Hematology, or European Society of Medical Oncology were also used to obtain any relevant data found which could contribute to the study.

Specialist Sources: An internet search was also performed and websites of the relevant organizations such as the American Society of Hematology, American Society of Clinical Oncology (ASCO), etc were also reviewed to identify and utilize any relevant information found.

 Search terms:

The following English Language search terms, as either text words or Medical Subject Headings (MeSH®), appearing in either the title, the abstracts or in the keywords list were used to identify relevant articles:

Erythropoietin, Epoetin, Cancer, Neoplasms, Chemotherapy, anemia, Quality of Life (QoL)

Inclusion Criteria:

• Relevant Subjects:
• Studies conducted amongst human subjects were included
• Studies conducted amongst adults (>18 years) were included
• Subjects with a histologically or clinically proven malignancy, irrespective of the severity of the disease (as assessed by the stage and grade of the disease)
• Studies where measures were taken to overcome potential confounders such as other potential causes of anemia, e.g. hemolysis, chronic blood loss, or iron deficiency
• Relevant Design:
• Randomized and nonrandomized but controlled trials of patients treated for CIA (ie, baseline Hb <11 g/dL)
• At least 10 patients per treatment group
• Type of Intervention: use of erythropoietin compared with the standard care (typically transfusions), placebo, or both
• Studies published in the English language

Study Quality Assessment and data extraction:

Two reviewers were appointed in order to independently scrutinize and review each study for quality assessment. Moreover, they were also required to carry out study selection and data extraction. If any disagreements arose amongst the two reviewers, a third party was involved to overlook the matter and settle the dispute via discussion. In order to assess the studies for their quality, various parameters were inspected including and not limited to randomization, concealment of allocation, blinding of patients and clinicians, documentation of dropouts and withdrawals, an intent-to-treat analysis.

Potential conflicts of interest and sources of support:

For this EBR, although no conflicts of interest were declared, potential conflicts of interest were managed via adopting a policy of full disclosure and transparency. Moreover, this evidence-based review is supported by the Ethics Review Committee (ERC).