Darbepoetin alfa in the treatment of chemotherapy-induced anaemia

Background: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA), with a longer half-life than previous recombinant human erythropoietins. After its initial development for anaemia due to renal insufficiency, an extensive clinical trial program has defined its role in cancer patients. Objective/methods: Review of the initial registration studies, further development and recent progress, guidelines for use in clinical practice (EORTC, ASCO/ASH), and specific focus on recent safety concerns. Results: Darbepoetin alfa significantly decreases the number of red blood cell transfusions in patients with chemotherapy-induced anaemia, and has been shown to improve health-related quality of life in several studies. The prolonged half-life allows a prolonged dosing interval. Administration every three weeks, a suitable schedule to synchronise with day 1 of many chemotherapy regimens, is as efficient as the initially registered weekly administration. Recent data strongly suggest that the addition of intravenous iron improves haemoglobin response rates. The use of these agents in clinical practice has to be according to the guidelines. Recent safety data reported a negative effect on survival when ESAs were used to treat anaemia that was either not chemotherapy related, or when used to maintain high levels of haemoglobin and prevent anaemia. All of these studies were not in accordance with existing guidelines, while safety data from clinical trials using ESAs according to the guidelines remain reassuring. Conclusion: Darbepoetin alfa has a well defined place in the treatment of chemotherapy-induced anaemia, and is safe when used in line with existing guidelines. Recent safety signals on cancer outcomes in studies not in accordance with these guidelines illustrate the need for further research into the complex interaction between anaemia and tumour hypoxia in cancer patients.     

Critiques of clinical guidelines in nephrology: anaemia

Chronic kidney disease (CKD) is characterised by reduced erythropoietin production and anaemia. The introduction in the late 1980s of recombinant human erythropoietin transformed the quality of life and the blood transfusion requirements of patients with advanced CKD, and several erythropoietin analogues or derivatives with the collective name of erythropoiesis-stimulating agents (ESAs) are now available. However, despite the treatment of hundreds of thousands of patients with ESAs there have still been relatively few randomised controlled trials comparing outcomes at pre-specified haemoglobin (Hb) concentrations. Several unanswered questions remain regarding the optimal use of ESAs, including the ideal target Hb level for an individual and a CKD population. The conclusion from the available interventional studies is that there is no evidence for a beneficial effect of complete correction of Hb and there is weak evidence of harm with an increase in cardiovascular events and mortality. This has prompted some renal advisory bodies to modify their guidance on ESA prescribing. This critique reviews current clinical guidelines and recommendations, their scientific basis, and identifies areas of controversy including the role of newer agents, the long-term safety of ESAs, the influence of the pharmaceutical industry, and the associated healthcare costs.     

The background and methodology of the Anaemia Cancer Treatment (A.C.T.) study: a global retrospective study of practice patterns and outcomes in the management of anaemia in cancer patients and their congruence with evidence-based guidelines

Goal The benefit of supportive care with erythropoiesis-stimulating agents (ESAs) for patients with cancer-related anaemia is well known. However, the European Cancer Anaemia Survey (ECAS, data from 2001) showed that about 60% of cancer patients with anaemia do not receive any treatment. Since ECAS, evidence-based guidelines have provided recommendations for ESA use, but it is not known to what extent current treatment patterns follow these guidelines. To address this issue, the Anaemia Cancer Treatment (A.C.T.) study was initiated. The background to the development of the A.C.T. study and study methodology are described. Materials and methods The A.C.T. study is a global, retrospective, pharmacoepidemiologic study of at least 2,560 medical records of anaemic patients with cancer who were previously treated with an ESA from a minimum of 186 centres. Records from patients aged greater than or equal to 18 years with a diagnosis of solid tumour or myeloma or lymphoma and who were started on ESAs 3–12 months before inclusion and followed for 8–10 weeks will be eligible. Factors associated with ESA non-responsiveness will also be evaluated. Main results Completion of the European phase of the study is anticipated in late 2007 with the rest of the world closing in late 2007 or early 2008. Publication of findings is anticipated in 2008. Conclusions By examining the extent to which anaemia management in clinical practice is congruent with best practice guidelines, the A.C.T. study will provide a further foundation for the development of evidence-based supportive cancer care.     

Deep exploration of PARP inhibitors in breast cancer: monotherapy and combination therapy

ObjectiveNearly 5% of patients with breast cancer carry germline BRCA mutations, which are more common in triple-negative breast cancer (TNBC). Previous clinical trials demonstrated the therapeutic efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) against BRCA-mutated metastatic breast cancer. The current study conducted a systemic review and meta-analysis of the clinical efficiency and safety of PARPis, either alone or combined with chemotherapy, in patients with TNBC.MethodsWe searched PubMed, EMBASE, and ClinicalTrials.gov to identify randomized controlled trials comparing PARPi therapy with chemotherapy, and comparisons of chemotherapy plus PARPis with chemotherapy alone were included. The study endpoints included the clinical response, progression-free survival, and adverse event rates.ResultsPARPi therapy was revealed to improve progression-free survival in patients with advanced breast cancer, either alone or in combination with chemotherapy. Subgroup analysis illustrated that patients with mutant BRCA1 and mutant BRCA2 and those who had not been treated with platinum-based agents could specifically benefit from PARPis.ConclusionPARPi monotherapy can significantly improve clinical outcomes in patients with advanced breast cancer, especially those with TNBC, those who had not previously received platinum therapy, and those with mutant BRCA1/2. PARPis combined with chemotherapy represent new treatment options for patients with advanced cancer.     

Use of darbepoetin alfa and epoetin alfa in clinical practice in patients with cancer-related anemia

Background: Patients with cancer may receive erythropoiesis-stimulating agents (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer-related anemia (CRA). DA and EA differ, however, with respect to their assumed duration of effect and thus their approved frequency of dosing, complicating direct comparison of their doses and costs. Objective: The objective of this study was to examine, from the perspective of a third-party payer, patterns of use and costs of DA and EA in patients with CRA, using episode-based methodology to account for differences in assumed duration of effect and frequency of dosing with these products. Methods: Using a large US health insurance claims database, we identified all patients with cancer who received ESAs between January 1, 2005, and June 30, 2005 (study period). For each such patient, we identified all unique episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and cost of ESA therapy within these EOCs, which were calculated using the ratio of total dose received and total cost of ESA therapy, respectively, to total EOC duration; only the first EOC for each patient was considered. EOCs were assumed to begin on the date of first ESA admin-istration within the study period, and end on the date of final ESA administration (within the episode) plus an assumed duration of effect based on the ESA received and corresponding dose. We also estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to control for differences in baseline characteristics of EA and DA patients. Results: We identified a total of 1226 patients with complete EOCs with ESAs (EA, 381; DA, 845). DA patients were more likely to have had evidence of receipt of chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P < 0.01). Estimated mean (95% CI) weekly dose within EOCs was 97 mug (94-99) for DA, and 43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment for differences in patient characteristics yielded a slightly lower ratio (403:1). Results were sen-sitive to the exclusion of EOCs consisting of a single administration of ESA therapy and/or the addition of an assumed duration of effect to the final ESA dose administered. Conclusions: Cost comparisons of DA and EA are sensitive to the assumed duration of effect added to the final dose of ESA therapy, especially for EOCs with relatively few administrations.     

一例广泛期小细胞肺癌的循证治疗

目的针对一例广泛期小细胞肺癌合并恶性胸水、肝转移的治疗问题,检索当前最佳临床证据,为患者恶性胸水的对症治疗和后续化疗方案提供依据。方法根据循证临床实践的PICO原则,提出问题,检索证据,对所获证据进行质量评价,并结合患者意愿制定治疗方案。结果共纳入10个随机对照试验,13个系统评价／Meta分析和3篇临床指南。证据结果表明：化疗能提高广泛期小细胞肺癌患者的生存率,艾迪注射液可以减轻放化疗所致的不良反应,提高患者的生存质量。EP方案是小细胞肺癌化疗最主要的标准化疗方案。结合患者情况,我们采用胸腔闭式引流术加经胸膜腔内注入博来霉素,待患者病情好转后,采用EP方案化疗,患者生存期要比广泛期小细胞肺癌的平均存活期长,生活质量得以提高,家属对治疗满意。结论广泛期小细胞肺癌患者以化疗为主,同时辅以对症、支持治疗,预防性头颅照射（PCI）可以减少脑转移的发生并提高患者生存率。     

Trends in anemia management in lung and colon cancer patients in the US Department of Veterans Affairs, 2002–2008

Purpose

In 2007, growing concerns about adverse impacts of erythropoiesis-stimulating agents (ESAs) in cancer patients led to an FDA-mandated black box warning on product labeling, publication of revised clinical guidelines, and a Medicare coverage decision limiting ESA coverage. We examined ESA therapy in lung and colon cancer patients receiving chemotherapy in the VA from 2002 to 2008 to ascertain trends in and predictors of ESA use.

Methods

A retrospective study employed national VA databases to “observe” treatment for a 12-month period following diagnosis. Multivariable logistic regression analyses evaluated changes in ESA use following the FDA-mandated black box warning in March 2007 and examined trends in ESA administration between 2002 and 2008.

Results

Among 17,014 lung and 4,225 colon cancer patients, those treated after the March 2007 FDA decision had 65% (lung OR 0.35, CI_95% 0.30–0.42) and 53% (colon OR 0.47, CI_95% 0.36–0.63) reduced odds of ESA treatment compared to those treated before. Declines in predicted probabilities of ESA use began in 2006. The magnitude of the declines differed across age groups among colon patients (p?=?0.01) and levels of hemoglobin among lung cancer patients (p?=?0.04).

Conclusions

Use of ESA treatment for anemia in VA cancer care declined markedly after 2005, well before the 2007 changes in product labeling and clinical guidelines. This suggests that earlier dissemination of research results had marked impacts on practice patterns with these agents.     

Extended administration of erythropoiesis‐stimulating agents for optimising the management of renal anaemia: what is the evidence?

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have transformed the management of anaemia in patients with chronic kidney disease (CKD), reducing transfusion requirements and leading to improved quality of life. However, effective anaemia management with current ESAs is labour-intensive and time-consuming. Approaches are required to simplify anaemia management and reduce the burden on healthcare systems. There is increasing interest in extending the administration interval of ESAs. This would result in considerable time-savings, reducing the workload of healthcare providers and potentially reducing healthcare system costs. Time saved could be utilised in improving other aspects of patient care, such as implementation of guidelines, or treating more patients. Potential benefits of extended administration intervals for patients include a less demanding regimen and fewer injections, which could lead to improved adherence to treatment. AIM: This article reviews studies of the efficacy of current ESAs in maintaining stable haemoglobin (Hb) levels when used at extended administration intervals of up to once monthly. SUMMARY OF FINDING: Patients who are already stable on more frequent ESA therapy and who respond well to treatment may be able to maintain stable Hb with extended dosing regimens with established ESAs. However, few patients with CKD currently receive ESAs once-monthly in clinical practice. New agents with long half-lives offer the potential for extended dosing regimens in all patients with CKD.     

Costs of care for lung and colon cancer patients receiving chemotherapy following FDA policy changes

Purpose

Use of erythropoiesis-stimulating agents (ESAs) in US cancer care declined amidst post-marketing evidence of adverse effects and the Food and Drug Administration’s (FDA) addition of a “black-box” warning to product labeling in March 2007. Because reduced ESA use may have led to more transfusions or increased anemia-related health care needs, we measured the policy’s impact on health care costs of lung and colon cancer patients receiving chemotherapy.

Methods

In a retrospective cohort study of 13,630 lung and 3,198 colon cancer patients in the Department of Veterans Affairs (VA) between 2002 and 2008, we calculated anemia treatment (ESA and transfusion), cancer- and non-cancer-related, and total health care costs for the chemotherapy episode of care. We used multivariable regression to examine health care costs and utilization between patients whose chemotherapy was administered before (PRE) or after (POST) March 1, 2007.

Results

ESA costs declined and transfusion costs were similar, resulting in lower overall POST-period anemia treatment costs (lung, $526 lower, P?P?P?P?Conclusions Although chemotherapy episode anemia treatment costs declined after the black-box warning, the savings were offset by increases in other cancer-related costs. Those increases were mainly in outpatient services and pharmacy, suggesting that likely drivers include adoption of new high-cost diagnostic approaches and therapeutic modalities. Additional research is needed to determine the effects of anemia management changes on patient outcomes and to more fully understand cost-benefit relationships in cancer treatment.     

Individual patient-versus literature-based meta-analysis of survival data: time to event and event rate at a particular time can make a difference, an example based on head and neck cancer

The objective of this study is to compare the results of an individual patient-based and a literature-based meta-analysis in chemotherapy in head and neck cancer and to identify the sources of difference. For all head and neck cancer randomized controlled clinical trials comparing chemotherapy and loco-regional treatment with loco-regional treatment alone, both the literature data and the individual patient data are retrieved and meta-analyses performed and compared. Only survival data are used as outcome, although both time to death and mortality at specific time points are considered in different analyses. There are substantial differences between the individual patient-based and the literature-based meta-analyses. The most important reason for the differing results is that the individual patient-based meta-analysis is based on a time to event analysis, whereas the literature-based meta-analysis is based on mortality at a specific time point. Mortality can change substantially with follow-up time. The absolute survival differences in the case study, for instance, increase from 2.6% at 2 years to 5.6% at 5 years.     

A new concept for the differential diagnosis and therapy of anaemia in cancer patients

Purpose

This study aimed to prove the usefulness of the diagnostic plot, using the haemoglobin content of reticulocytes as a measure of functional iron deficiency (FID) and the ferritin index as a measure of iron availability, to customise anaemia treatment in cancer patients.

Methods

Based on results of this plot, cancer patients fulfilling practice guideline criteria to receive erythropoiesis-stimulating agents (ESAs) were allocated to treatment with ESAs alone, iron alone or the combination of both. Primary endpoint was the percentage of patients identified to require iron in addition or as an alternative to ESA therapy.

Results

Out of 303 patients screened, 286 were allocated to treatment: 204 patients were normochromic and iron replete and treated with ESAs alone, 22 had both FID and anaemia of chronic disease and were treated with ESAs and parenteral iron, and 60 were iron-depleted and treated with iron only. After 8?weeks, a haemoglobin increase >1?g/dL from baseline was shown by 56% of patients treated with ESAs alone, by 100% of patients receiving the combination, by 50% of normochromic and by 73% of hypochromic iron-depleted patients receiving iron only. Acute phase reaction did not diminish the response rate to ESAs.

Conclusions

The diagnostic plot was superior to transferrin saturation and ferritin in predicting iron availability in hypochromic patients treated with ESAs and proved useful to select treatment for anaemia in cancer patients.     

Synchronization of administrations of chemotherapy and erythropoiesis-stimulating agents and frequency of associated healthcare visits

Purpose

The erythropoiesis-stimulating agents (ESAs), darbepoetin alfa (DA), and epoetin alfa (EA) differ with respect to dosing schedule in chemotherapy-induced anemia. DA can be administered less frequently than EA, which may increase synchronicity between chemotherapy and ESA schedules. This study compared DA and EA with respect to frequency of synchronization and frequencies of total and ESA healthcare visits in current clinical practice.

Methods

A retrospective analysis of ESA utilization during ESA episodes of care was conducted on all cancer patients identified in the SDI health oncology electronic medical records database who underwent chemotherapy and received ESA therapy from July 1, 2007 to March 31, 2010 (n?=?6522 DA, n?=?3,439 EA).

Results

The frequency of synchronization (chemotherapy and ESA therapy on the same day) was higher with DA (67 %) than EA (58 %) (p?<?0.001). The odds that an ESA administration was synchronized with chemotherapy were higher with DA compared with EA (odds ratio?=?1.46, 95 % CI: 1.37, 1.54). Compared with EA, DA patients had 2.3 fewer visits with an ESA administration (p?<?0.001) and 3.0 fewer total visits (p?<?0.001).

Conclusions

Compared with patients receiving EA, DA patients were more likely to have an ESA administration on the same healthcare visit as chemotherapy and had fewer visits for any cause or for ESA administration. These results suggest that through greater synchronization of ESA and chemotherapy administrations, DA may reduce patient and practice burden and healthcare utilization.     

Anemia as a risk factor for CKD and CVD

Chronic kidney disease (CKD) is now recognized as a risk factor of both end-stage renal disease (ESRD) and independently cardiovascular disease (CVD). Therefore, a specific renoprotective intervention is strongly recommended, including blood pressure control as well as anemia improvement with erythropoietin stimulating agents (ESAs). Treatment of renal anemia with ESAs has been proved to improve quality of life (QOL) and finally reduce patient mortality. Recently, Silverberg, et al. created a novel clinical entity of Cardio-Renal Anemia (CRA) syndrome, in which anemia plays a key role for worsening both CKD and cardiac performance in a vicious circle. An appropriate and vigorous treatment of anemia has now been accepted to terminate or weaken the circle. Recently, two large-scaled randomized controlled trials were reported, being the CREATE (cardiovascular risk reduction by early anemia treatment with epoetin beta) study and the CHOIR (correction of hemoglobin and outcomes in renal insufficiency) study. They demonstrated that early initiation of ESA treatment and targeting at higher hemoglobin level (near normal level) failed to show the lowering effects for cardiovascular events as compared to a group in which Hb targeting was lower (sub-normal level) in pre-dialysis CKD patients. While there has been many argues in these reports especially about baseline patients characteristics, being a quite high incidence of severe cardiovascular co-morbidity. Thus, further evidences should be accumulated to resolve a proper target level of Hb in ESA treatment.     

Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis

Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).     

The Association of Quality of Life and Survival in Cancer Patients

Abstract

The incorporation of 'targeted therapies' into standard cancer care has changed how clinicians treat cancer. Small molecule inhibitors, antibodies, and conjugated agents target cancer cells more specifically than traditional chemotherapy. These therapies can be used alone or in combination with chemotherapy in first-line, refractory, or relapsed settings. Although designed to spare normal tissue, these agents do have systemic toxicity. Notably, their toxicity profiles are distinct from those encountered with chemotherapy. These agents have demonstrated efficacy in terms of improved tumour response, survival, symptom control, and/or quality of life. Cancer treatment will continue to change as additional targeted agents are evaluated in clinical trials and are brought into standard medical care. The palliative care clinician is likely to encounter these agents with increasing frequency, making decisions to continue or discontinue therapy, adding targeted agents to improve symptoms, performance status, or quality of life, or advising patients to return to their oncologists for further advice as new agents become available. Presented here, Part 1 of this review focuses on small molecules. All but one of these agents are oral, and they are all relatively well tolerated. In the future, Part 2 will introduce antibodies and conjugated agents.     

Adjuvant chemotherapy in oesophageal cancer: a meta-analysis and experience from the Shanghai Cancer Hospital

Whether adjuvant chemotherapy increases survival of oesophageal cancer patients has been widely debated. The present study used meta-analysis software to combine data from six studies up to July 2007 that were found and selected as suitable, comprising a total of 1001 oesophageal cancer patients. The results indicated that adjuvant chemotherapy did not significantly improve outcome in oesophageal cancer patients. A trend towards improved outcome from adjuvant chemotherapy was found in lymph node-positive patients, but did not reach significance. In our own study including 270 oesophageal cancer patients, adjuvant chemotherapy did not improve overall patient survival, but did improve survival for patients with metastases in cervical and/or celiac lymph nodes (stage IVa). Although our study had the largest patient sample, more prospective clinical trials with large numbers of patients are necessary to confirm the value of adjuvant chemotherapy in stage IVa patients.     

Management of adverse reactions caused by cancer chemotherapy in elderly patients

With the prolongation of life expectancy in Japan, cancer is increasing in the elderly. Several retrospective studies have shown that the frequency of toxicity, response to chemotherapy and overall survival are similar in elderly and younger patients with cancer with good performance status. However, because many investigators have arbitrarily excluded elderly patients from clinical trials and there have been a few clinical trials for elderly patients with cancer, no standard treatment in the elderly has been established for most cancer. New therapeutic strategies are clearly needed to prolong survival, and to improve quality of life in elderly patients with cancer.     

紫杉醇治疗小细胞肺癌的系统评价

目的系统评价紫杉醇在小细胞肺癌治疗中的临床疗效和安全性。方法采用Cochrane系统评价方法，检索Cochrane图书馆临床对照试验资料库、MEDLINE、EMbase、CBM、CNKI和VIP等电子数据库，检索时间截至2007年。纳入含紫杉醇治疗小细胞肺癌的对照研究。由2名评价者独立评价并交叉核对纳入研究质量，对同质研究采用RevMan 4．2．2软件进行Meta分析。结果共纳入9个对照研究，1675例小细胞肺癌患者，5个研究报道采用了随机方法，9个研究均未详细报道是否采用盲法。Meta分析结果表明，PET方案（紫杉醇十顺铂＋足叶乙甙）与EP方案（顺铂十足叶乙甙）的反应率相似[OR=1．35，95％CI（0．98，1．85）]，PET方案化疗后重度血小板下降[OR=I．68，95％CI（1．12，2．52）]和致死性毒性[OR=4．00，95％CI（1．77，9．04）]高于EP方案，而化疗后重度白细胞下降低于EP方案[OR0．50，95％CI（0．37，0．68）]。所有研究共报道了54例治疗相关性死亡。结论在小细胞肺癌的一线治疗中，紫杉醇与卡铂、足叶乙甙合用可提高无进展生存期，但与EP方案合用并不能提高长期生存率且增加了毒性，紫杉醇作为二线用药有一定疗效。由于本系统评价纳入的研究数量较少，存在偏移的高度可能，影响了结果的论证强度，期待更多高质量的随机双盲对照试验以提供高质量的证据。     

CONFERENCE REPORT: Can intravenous iron therapy meet the unmet needs created by the new restrictions on erythropoietic stimulating agents?

In 2008, after reports of an association between erythropoietic stimulating agent (ESA) therapy and the potential for either thrombotic cardiovascular events or more rapid tumor progression in some cancers, the Food and Drug Administration changed the product labeling for ESAs, adding a black box warning as well as more restrictive indications, especially in oncology patients. In addition the Centers for Medicare and Medicaid Services has placed significant restrictions on payments for ESA therapy. These new limitations on ESA have led to increased use of transfusions in anemic cancer patients. This increase in allogeneic transfusions potentially will place an additional burden on the US blood supply. Although allogeneic blood transfusion is one answer to ESA restrictions, the use of intravenous iron therapy (IV iron) is another possible alternative. We will discuss the use of IV iron as primary therapy for anemia, the use of combination IV iron and ESA therapy to improve efficiency and decrease costs, and evidence that IV iron with and without ESA therapy can reduce allogeneic blood transfusions in surgical patients. We will also review the available IV iron agents and their comparative safety profiles.     

Hematologic outcomes and blood utilization in cancer patients with chemotherapy-induced anemia (CIA) pre- and post-national coverage determination (NCD): results from a multicenter chart review

Purpose

In July 2007, the Centers for Medicare and Medicaid Services (CMS) limited coverage of erythropoiesis-stimulating agents (ESAs) in cancer patients with chemotherapy-induced anemia (CIA) through a National Coverage Determination (NCD). The primary objective of this study was to compare transfusion rates in patients with CIA with lung, breast, or colorectal cancer before and after the NCD.

Methods

Adult Medicare patients with CIA treated at 49 community oncology clinics were selected from two time periods based on clinics' NCD implementation date. Chart data were abstracted for 12?weeks post-CIA episode start, defined as hemoglobin (Hb) level <11?g/dL while receiving chemotherapy or within 60?days of the last chemotherapy dose. Multivariate analyses were used to calculate the odds of transfusion and to assess the units of blood transfused, controlling for differences in demographics, clinical history, and chemotherapy.

Results

Eight hundred pre-NCD and 994 post-NCD patients from 49 sites were selected. Of the patients, 56% used ESAs post-NCD vs. 88% pre-NCD (p?p?p?=?0.0238) and increased blood utilization of 53% (units transfused: OR 1.53, 95% CI 1.15–2.04, p?=?0.0034).

Conclusions

Decreased frequency and duration of ESA administration were reported in the post-NCD vs. pre-NCD period. Findings were accompanied by a modest but statistically significant increase in transfusions and a decrease in Hb values.