Anemia Management Using Erythropoiesis-Stimulating Agents and Iron Therapy: Development and Implementation of an Evidence-Based Learning Needs Assessment

Advance practice nurses play a critical role in the assessment and management of patients with chemotherapy-induced anemia. Although the use of erythropoiesis-stimulating agents (ESAs) has been very effective in treating chemotherapy-induced anemia, approximately 30% to 50% of cancer patients receiving ESAs do not achieve a clinically meaningful hematologic response.¹ Recent prospective, controlled trials have demonstrated the benefits and marked synergy of the addition of intravenous (IV) iron supplementation to ESA therapy in patients with documented iron deficiency and chemotherapy-induced anemia.^2-5

The 2001 Medicare data show that measured iron parameters and the use of IV iron supplementation both increased significantly in nephrology patients over the previous decade. In oncology, however, the approach to identifying and treating iron deficiency is far less evolved. In fact, the same 2001 Medicare data show that the use of IV iron remained stagnant, and obtaining iron parameters regressed considerably in oncology patients.⁶ In response to these reported discrepancies, a Learning Needs Assessment was developed to assess the knowledge of oncology and nephrology nurses regarding iron indices and treatment of iron-deficiency anemia to identify potential barriers to anemia management in current oncology practices.

Learning Needs Assessment

The Learning Needs Assessment was conducted by administering an Iron Knowledge Nursing Questionnaire to evaluate several aspects of the practices of both nephrology and oncology nurses who identify and manage patients with iron-deficiency anemia. The questionnaire assessed education background and work setting, laboratory markers utilized to determine iron status, treatment of anemia and iron deficiency, and challenges associated with IV iron administration. Nephrology nurses were used as a comparator, because nephrology practices have extensive experience managing anemia, especially using IV iron in conjunction with ESA therapy.⁷

Survey data were collected from 165 nurses attending Oncology Nursing Society (n = 85) and American Nephrology Nursing Association (n = 80) chapter meetings. Iron Knowledge Nursing Questionnaires were distributed at these meetings between June 2007 and June 2008. Data are reported as the number and percent of respondents selecting each answer.

Survey results

The survey results show the largest disparity between oncology and nephrology nurses in the following areas:

• Understanding and appropriate use of iron indices to assess iron deficiency, including interpreting laboratory values for functional and absolute iron deficiency
• Use of IV versus oral iron supplementation in conjunction with ESA therapy for iron-deficiency anemia
• Perception of safety and administration challenges with the use of IV iron.

Oncology nurses most commonly report and assess iron deficiency using serum ferritin, total iron-binding capacity (TIBC), and/or serum iron. However, less than 50% of the oncology nurses correctly defined these measurements. Nephrology nurses most commonly report and assess iron deficiency using transferrin saturation (TSAT) and serum ferritin, and they had a greater ability to correctly define these terms (Figure 1). Approximately one third of oncology nurses reported that iron studies are ordered before ESA therapy, whereas nephrology nurses generally order iron studies on admission and monthly thereafter.

Treatment interventions differ among the practices of oncology and nephrology nurses. About 47% of oncology nurses reported that their anemic, ESA-treated patients receive oral iron or no iron supplementation at all. Only 18% reported that their patients are treated with the addition of IV iron therapy only. This is in contrast to nephrology nurses; 79% reported that treatment for anemic, ESA-treated patients is with IV iron only (Figure 2). When iron deficiency is diagnosed, the most commonly prescribed treatment for cancer patients is oral iron (54% of oncology nurse respondents), whereas IV iron is frequently ordered for nephrology patients (91% of nephrology nurse respondents).

Approximately 87% of nephrology nurses versus 20% of oncology nurses treat functional iron deficiency with ESA and IV iron therapy combined. Oncology nurses are more likely to use ESA therapy alone (35%) or ESA plus oral iron therapy (31%).

The perception of the challenges surrounding IV iron use differs between nephrology and oncology nurses. In oncology, adverse reactions and administration of IV iron were reported as the biggest concerns (54% and 40%, respectively). Nephrology nurses reported iron markers and guidelines as the biggest challenges to using IV iron therapy.

The results from this survey demonstrate a significant need for oncology nursing educational programs. To optimize the care of oncology patients, it is crucial that educational programs focus on the following areas:

• Anemia assessment with laboratory values and iron indices
• Anemia management with emphasis on the clinical advantages of IV iron in cancer patients
• Anemia treatment monitoring in accordance with current practice guidelines for timely evaluation of iron studies.

Iron indices

A strong working knowledge of iron indices is essential in the proper assessment and subsequent treatment of irondeficiency anemia. The survey results showed that less than half of the oncology nurses surveyed could properly define iron laboratory terms.

TSAT and serum ferritin are commonly used iron indices to assess anemic patients. However, recognizing their limitations is essential in understanding the clinical status of a patient. Iron exists in the body either in storage or as a labile form, ready to be used in the production of red blood cells (RBCs). Transferrin is an iron transport protein, which brings iron from its stored areas in the reticuloendothelial system (RES) to the bone marrow to be available for incorporation into RBCs. TIBC describes how much transferrin is available to which iron can bind. TSAT represents functional iron, estimating how saturated transferrin is with iron. TSAT levels provide clinicians with an idea of how much iron is readily available to the bone marrow for erythropoiesis. It is calculated using serum iron levels and TIBC ([serum iron divided by TIBC] x 100).

Serum ferritin is used as an indirect marker of iron stores. Tissue ferritin is the major iron-storage protein found primarily in the RES. Tissue ferritin is a protein shell made of polypeptide units surrounding an iron core. It acts as part of the mechanism to regulate iron status by storing iron in the RES when too much iron exists in the blood or releasing iron into the blood when iron deficiency occurs. When iron binds to tissue ferritin to be stored, serum ferritin is released into the plasma. Although the relationship of iron stores and tissue ferritin is well defined, the relationship of serum ferritin and iron status is not as clear. The small quantities of ferritin found in the serum do not play a role in the storage of iron. Unlike tissue ferritin, serum ferritin contains little to no iron, making it a less than perfect indicator of iron stores.^8-10

The key to proper interpretation of iron indices is understanding the role of inflammation and ESA therapy itself. Inflammatory cytokines, which can be chronically present in malignancy and other chronic diseases such as kidney disease, alter the production of transferrin and serum ferritin.⁸ Serum ferritin reflects iron in storage. In the presence of inflammation, however, serum ferritin levels can be elevated, requiring a review of the overall clinical picture of the patient to determine if the elevated ferritin level reflects high storage levels or inflammation.¹¹

Low serum ferritin (<100 ng/mL) is indicative of absolute iron deficiency or depleted iron stores. However, the impact of inflammation on ferritin can often be seen in functional iron deficiency, in which TSAT is low (<20%) but serum ferritin is elevated (>100 ng/dL). Oftentimes, IV iron is not considered in these patients, because the elevated serum ferritin is attributed to adequate or excess iron in storage. Inflammation’s impact on serum ferritin needs to be part of the assessment. The low TSAT in these patients reflects inadequate amounts of iron for erythropoiesis. In addition, ESA therapy drives the need for iron, which can also contribute to functional iron deficiency. In one study, almost two thirds of anemic patients about to start a cycle of chemotherapy had either functional or absolute iron deficiency at the time of enrollment (Table).¹²

The American Society of Hematology/American Society of Clinical Oncology Clinical Practice Guidelines recommend conducting baseline and periodic monitoring of iron studies.¹³ The National Comprehensive Cancer Network (NCCN) Guidelines for Cancer- and Chemotherapy-Induced Anemia recommend conducting iron studies as part of the screening evaluation for anemia and prior to the initiation of ESA therapy.¹⁴ Despite these guidelines, only one third of oncology nurses surveyed stated that iron indices are evaluated prior to ESA therapy, and just 23% revealed that iron studies are checked on admission and periodically thereafter. Educating oncology nurses on the proper assessment and follow-up monitoring of their anemic patients could help to ensure adequate identification of iron-deficiency anemia in cancer patients.

Use of IV iron

Several prospective, randomized, controlled trials have been conducted to evaluate the efficacy of IV iron supplementation in combination with ESA therapy in treating iron deficiency in oncology patients.^2-5 In patients with iron-deficiency and chemotherapy- related anemia, these studies demonstrated that the addition of IV iron to ESA therapy results in increased hemoglobin responsiveness,^2-4 faster time to response,⁴ decreased transfusion requirements,^4,5 and improved quality of life, energy, and activity.³ In all of these studies, oral iron was used in the control arm and IV iron demonstrated superior efficacy compared with oral iron. The effect of oral iron on hemoglobin was shown to be similar to using no iron at all in cancer patients.^2,3

The NCCN and European Organisation for Research and Treatment of Cancer guidelines recommend the use of IV iron products for iron repletion in cancer patients with absolute iron deficiency. These guidelines further state that IV iron should be considered for the treatment of functional iron deficiency for patients receiving ESAs. They also recognize that oral iron is less effective, supported by recent studies demonstrating that IV iron is superior to oral iron. In addition to poor efficacy, the gastrointestinal side effects of oral iron are often intolerable for patients.^14,15

Despite this clinically significant information, 47% of oncology nurses surveyed treat anemic ESA-treated patients with oral or no iron. Recognizing the substantial benefit of IV iron over oral iron in the oncology setting could optimize treatment strategies and clinical outcomes in iron-deficient, anemic cancer patients.

Conclusion

This Learning Needs Assessment compared the practice patterns of nephrology nurses with oncology nurses to reveal areas of opportunity for education and optimization of anemia management in oncology. Lessons learned from nephrology nurses include the need for increased understanding of iron indices, proper use of IV versus oral iron, and education regarding safety and administration.

References

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14. National Comprehensive Care Network. Clinical Practice Guidelines in Oncology: Cancer- and Chemotherapy-Induced Anemia. V.3.2.2010. www.nccn.org/professionals/physician_gls/PDF/anemia.pdf. Accessed May 30, 2010.

15. Bokemeyer C, Aapro MS, Courdi A, et al; for the European Organisation for Research and Treatment of Cancer (EORTC) Taskforce for the Elderly. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer. 2007;43:258-270.