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The Oncologist, Vol. 9, No. 4, 451–458, July 2004
© 2004 AlphaMed Press

Effectiveness of Darbepoetin Alfa Versus Epoetin Alfa in Patients with Chemotherapy-Induced Anemia Treated in Clinical Practice

Jeffrey Pattona, Timothy Reevesa, Joel Wallaceb

a Tennessee Oncology, Nashville, Tennessee, USA; b Amgen Inc., Thousand Oaks, California, USA

Correspondence: Jeffrey Patton, M.D., Tennessee Oncology, 397 Wallace Road, Suite 201, Nashville, Tennessee 37211-8025, USA. Telephone: 615-333-2481; Fax 615-781-3923; e-mail: jpatton{at}tnonc.com


   ABSTRACT
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 Additional Reading
 
Primary Purpose. The objective of this retrospective observational cohort study was to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in patients with chemotherapy-induced anemia using data from noncontemporaneous chart audits conducted at a community-based oncology practice.

Materials and Methods. For the first chart audit, data were collected from consecutive patients with nonmyeloid malignancies with diagnoses of chemotherapy-induced anemia and hemoglobin levels ≤10.5 g/dl who were receiving concurrent chemotherapy and had at least 5 weeks of visits from July-September 2000. After therapeutic substitution of darbepoetin alfa for epoetin alfa for all patients with chemotherapy-induced anemia, data were collected from consecutive darbepoetin alfa-treated patients with diagnoses of chemotherapy-induced anemia and at least 8 weeks of visits from June-October 2002 (darbepoetin alfa was approved in July 2002).

Results. Most (86%) of the 212 epoetin alfa-treated patients had received an initial dose of 40,000 U once weekly, and most (85%) of the 196 darbepoetin alfa-treated patients had received a fixed dose of either 100 µg once weekly (49%) or 200 µg every 2 weeks (36%). At 8 weeks, the mean change in hemoglobin level was 1.1 g/dl for the darbepoetin alfa patient group and 1.0 g/dl for the epoetin alfa patient group.

Discussion. Utilization, dose escalation rates, and clinical outcomes were considered comparable for the darbepoetin alfa and epoetin alfa patient groups.

Conclusions. Darbepoetin alfa, 100 µg once weekly or 200 µg every 2 weeks, appears to be as effective as epoetin alfa, 40,000 U once weekly, for the treatment of chemotherapy-induced anemia in the clinical practice setting.

Key Words. Darbepoetin alfa • Epoetin alfa • Erythropoietin • Anemia • Neoplasms


   INTRODUCTION
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 Additional Reading
 
Anemia is one of the most common complications in cancer patients receiving chemotherapy [1]. Erythropoietic proteins including epoetin alfa, epoetin beta (known collectively as recombinant human erythropoietin [rHuEPO]), and darbepoetin alfa have been widely adopted for the management of chemotherapy-induced anemia. Darbepoetin alfa is a unique erythropoietic protein with an approximately threefold longer half-life than rHuEPO, allowing less frequent dosing [2–4]. Darbepoetin alfa was recently approved for the treatment of chemotherapy-induced anemia; therefore, practitioners are now in the process of evaluating the most effective dose and schedule of this agent in clinical practice, as well as its effectiveness relative to epoetin alfa. This report describes an evaluation of erythropoietic agents conducted at Tennessee Oncology, a network of 30 private practice physicians at 25 community-based oncology clinics.

Epoetin alfa, administered one to three times weekly, has been evaluated against placebo in several randomized controlled trials and has also been studied in several uncontrolled studies in patients with chemotherapy-induced anemia [5–10]. The starting dose of epoetin alfa generally used in our network is 40,000 U weekly (QW) with a dose increase to 60,000 U in patients with inadequate responses, as per standard clinical practice in the U.S. The epoetin alfa dose is to be increased at week 5 for a patient failing to achieve at least a 1-g/dl increase from their baseline hemoglobin level and is to be decreased by 25% if a patient’s hematocrit reaches 36% or if their hemoglobin level reaches 12 g/dl.

Darbepoetin alfa, administered every 1, 2, 3, or 4 weeks, has been evaluated in several randomized placebo- or active-controlled trials in patients with chemotherapy-induced anemia [11–15]. In determining the starting dose of darbepoetin alfa for the network guidelines, we considered the minimum effective dose of 1.5 µg/kg QW and the comparable every-2-week (Q2W) dose of 3 µg/kg [4, 11]. For convenience, physicians were advised to administer these doses as fixed doses of 100 µg QW or 200 µg Q2W based on an average patient weight of 70 kg. The dose titration rules for darbepoetin alfa dose changes are the same as those listed above for epoetin alfa.

The objective of this retrospective observational cohort study was to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in patients with chemotherapy-induced anemia using data obtained from noncontemporaneous chart audits conducted at a community oncology practice.


   MATERIALS AND METHODS
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 Additional Reading
 
Patients
Two chart audits were conducted from consecutive series of adult cancer patients with diagnoses of chemotherapy-induced anemia. The first audit included patients who met the following inclusion criteria: diagnosed with a nonmyeloid malignancy, receiving concurrent chemotherapy, anemic (baseline hemoglobin level ≤10.5 g/dl), diagnosed with chemotherapy-induced anemia (V58.1), and had at least 5 weeks of visits from July-September 2000. Data were collected through a maximum 8 weeks of treatment. As one intent of this audit was to evaluate whether epoetin alfa was being appropriately prescribed, receipt of epoetin alfa was not an inclusion criterion, and data were collected on all patients considered eligible for erythropoietic therapy. The requirement for at least 5 weeks of data was specified based on the primary focus of determining drug use. For patients receiving epoetin alfa, data were collected from the time of the first epoetin alfa dose. All patient and physician identification information was blinded to maintain confidentiality.

After a network-wide therapeutic substitution of darbepoetin alfa (approved for chemotherapy-induced anemia in July 2002) for epoetin alfa for all patients with chemotherapy-induced anemia, a second chart audit was performed. For this second audit, patients who met the following inclusion criteria were selected by cross-referencing: received darbepoetin alfa (code J3490), diagnosed with chemotherapy-induced anemia (V58.1), and had at least 8 weeks of visits from June-October 2002. Data were collected from the time of the first darbepoetin alfa dose. All patient and physician identification information was blinded to maintain confidentiality.

Data Collection
Treatment data collection variables included: hemoglobin concentration at baseline; initial dose and schedule of erythropoietic protein administered; hemoglobin concentration for darbepoetin-alfa-treated patients over weeks 1–8; hemoglobin concentration for epoetin-alfa-treated patients at week 1 and from weeks 5–8; and red blood cell transfusion requirements including hemoglobin at the time of the transfusion, number of transfusions, and volume transfused.

End Points
End points for this analysis included usage patterns and clinical outcomes associated with each erythropoietic protein. Usage patterns included: the initial dose distribution and frequency; the proportion of patients requiring a dose increase at week 5; and the proportion of patients requiring a dose reduction. Clinical outcomes included red blood cell transfusion requirements and change in hemoglobin level at 5 and 8 weeks after the initiation of treatment.

Analytical Methods
The analysis sets for this study included all patients treated with a single erythropoietic agent (all epoetin alfa patients versus all darbepoetin alfa patients; patients who had not received an erythropoietic protein or who had received both agents were not included) and the most common starting dose subsets of the All Patients dataset (epoetin alfa, 40,000 U QW; darbepoetin alfa, 100 µg QW; and darbepoetin alfa, 200 µg Q2W). The primary analysis for hemoglobin change over time was an intent-to-treat analysis in which missing hemoglobin values and hemoglobin values within 28 days of transfusion were imputed by carrying forward the last nonmissing or pretransfusion value. This analysis was conducted for the All Patient dataset and for the Most Common Starting Dose dataset. Several sensitivity analyses were also performed. One of these was the primary analysis without adjustment for transfusions (intent-to-treat analysis in which missing hemoglobin values were imputed by carrying forward the last nonmissing value; hemoglobin values within 28 days of transfusion were included in the analysis); this analysis was conducted for the All Patient dataset. Two additional sensitivity analyses were performed in subgroups of the Most Common Starting Dose dataset (patients with 8 weeks of visits; patients with baseline hemoglobin levels ≤10.5 g/dl) to evaluate the effects of the differing entry criteria on the results of the analyses. Both of the latter sensitivity analyses were conducted with the same methodology as the primary analysis (intent-to-treat analysis; missing values and values within 28 days after transfusion were imputed by carrying the last nonmissing or pretransfusion value forward).


   RESULTS
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 Additional Reading
 
Patient Population
In the first chart audit, data were collected on 322 patients from 20 physicians. Of these, 212 patients were treated with epoetin alfa and 110 had not received erythropoietic therapy. No differences in demographic or disease characteristics were noted between the patients who received epoetin alfa and those who did not. Only those treated with epoetin alfa were included in this analysis. In the second chart audit, data were collected on 300 patients from 21 physicians. Of these, 196 were treated with darbepoetin alfa only and 104 had received both epoetin alfa and darbepoetin alfa. Only those treated with darbepoetin alfa only were included in this analysis. Therefore, the 408 patients included in this retrospective cohort study comprised 212 patients treated with epoetin alfa and 196 patients treated with darbepoetin alfa.

Baseline demographics and disease characteristics were generally similar for the epoetin alfa-treated and the darbepoetin alfa-treated patients (Table 1Go). Patients in the darbepoetin alfa group were slightly younger than those in the epoetin alfa group (mean age 65 versus 69 years, respectively). Slightly more than half the patients in both groups were women, at 55% and 62% for the darbepoetin alfa and epoetin alfa groups, respectively. In general, the distribution of tumor types in the treatment groups was similar, although there was a larger proportion of patients with lymphoma in the epoetin alfa group (21% versus 9%) and a larger proportion of patients with lung cancer in the darbepoetin alfa group (31% versus 17%).


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  		Table 1. Baseline demographics and disease characteristics
 
The mean (95% confidence interval [CI]) baseline hemoglobin level for the epoetin alfa-treated patients was 9.6 g/dl (9.5–9.7), and 89% of those patients had baseline hemoglobin levels ≤10.5 g/dl. The mean (95% CI) baseline hemoglobin level for the darbepoetin alfa-treated patients was 10.1 g/dl (10.0–10.2), and 79% of those patients had baseline hemoglobin levels ≤10.5 g/dl. The mean (95% CI) baseline hemoglobin levels for the 200 µg Q2W darbepoetin alfa dose group (n = 70) and the 40,000 U QW epoetin alfa dose group (n = 183) were similar, at 9.9 g/dl (9.7–10.1) and 9.7 g/dl (9.6–9.8), respectively (Table 2Go).


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  		Table 2. Baseline hemoglobin
 
Usage Patterns
Most (85%) patients treated with darbepoetin alfa received an initial fixed dose of 100 µg QW (49%) or 200 µg Q2W (36%). The initial dose and schedule of the majority of patients (86%) in the epoetin alfa dose group was 40,000 U QW (Fig. 1Go). At week 5, 14% of all darbepoetin alfa-treated patients received dose increases, compared with 24% of all epoetin alfa-treated patients (Table 3Go). The proportion of patients in each group who should have received a dose increase based on meeting the criterion of a <1-g/dl increase in hemoglobin after 4 weeks of treatment was approximately 50% in each group. In the 100 µg QW and 200 µg Q2W darbepoetin alfa dose groups, the rate of dose increase was lower for those who had received the longer dosing interval, indicating that less frequent dosing had no impact on overall dose requirements. The proportions of patients who received dose decreases were similar across both drugs and all dose groups.



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  		Figure 1. Percentages of patients treated with darbepoetin alfa (A) and epoetin alfa (B) by starting dose and schedule.

 

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  		Table 3. Frequency of dose increases and decreases
 
RBC Transfusions
The incidence of transfusion was slightly lower for all darbepoetin alfa-treated patients (7%) than for all epoetin alfa-treated patients (15%) (Table 4Go). Transfusion rates were similar for the darbepoetin alfa 200 µg Q2W group and the epoetin alfa 40,000 U QW group (11.4% versus 13.7%, respectively). Of those who received transfusions, more epoetin alfa patients received large transfusion volumes (>4 units) than did darbepoetin alfa patients (28% versus 0%).


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  		Table 4. Incidence of RBC transfusion
 
Change in Hemoglobin

All Patients
The mean (95% CI) changes in hemoglobin level for the All Patient groups were 0.8 g/dl for darbepoetin alfa and 0.6 g/dl for epoetin alfa at 5 weeks (Table 5Go). At 8 weeks, the mean changes in hemoglobin level were 1.1 g/dl and 1.0 g/dl, respectively.


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  		Table 5. Mean (95% CI) change in hemoglobin level (g/dl) from baseline: all patients
 
A sensitivity analysis was done to evaluate the effects of transfusion on the mean change in hemoglobin level (Table 5Go). This analysis showed that transfusions inflated the mean change in hemoglobin value by 0.1 g/dl for darbepoetin alfa and by 0.3 g/dl for epoetin alfa at week 5. The greater impact of transfusions on the mean change in hemoglobin level for the epoetin alfa group relative to the darbepoetin alfa group was expected based on the higher incidence of transfusion in this group, as well as the higher proportion of patients receiving large transfusion volumes (Table 4Go). At 8 weeks, the inflation due to transfusions was 0.1 g/dl for both the darbepoetin alfa and epoetin alfa patient groups.

Most Common Starting Dose Groups
Mean change in hemoglobin level was also calculated for each of the most common starting dose groups. Darbepoetin alfa, administered at 100 µg QW or 200 µg Q2W, resulted in greater observed mean changes in hemoglobin level at 5 weeks and 8 weeks than epoetin alfa, administered at 40,000 U QW (Fig. 2Go). At 5 weeks, the mean changes in hemoglobin level for the darbepoetin alfa 100 µg QW and 200 µg Q2W dose groups were both 0.8 g/dl, compared with a mean change of 0.6 g/dl for the epoetin alfa 40,000 U QW dose group. At 8 weeks, the mean change in hemoglobin level for the darbepoetin alfa 100 µg QW and 200 µg Q2W dose groups were 1.1 g/dl and 1.3 g/dl, respectively, compared with a mean change of 0.9 g/dl for the epoetin alfa 40,000 U QW dose group.



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  		Figure 2. Mean (95% CI) change in hemoglobin level by most common starting dose group. Data at weeks 5 and 8 are shown for the darbepoetin alfa 100 µg QW, darbepoetin alfa 200 µg Q2W, and epoetin alfa 40,000 U QW groups. Intent-to-treat analysis; missing values and values within 28 days after transfusion were imputed by carrying the last nonmissing or pretransfusion value forward.

 

Sensitivity Analyses
Sensitivity analyses designed to address differences in patient selection criteria for the epoetin alfa-treated versus darbepoetin alfa-treated patients were conducted. In the subset of patients with 8 weeks of data (selection criterion for darbepoetin alfa patients, but not for epoetin alfa), the mean change in hemoglobin level was similar to that found in the primary analysis.

A baseline hemoglobin level ≤10.5 g/dl was a selection criterion for epoetin alfa but not for darbepoetin alfa; however, this resulted in only a 10% difference between the two groups (proportions of patients with baseline hemoglobin levels ≤10.5 g/dl were 89% in the epoetin alfa group and 79% in the darbepoetin alfa group). A sensitivity analysis including only the subset of patients with baseline hemoglobin levels ≤10.5 g/dl was conducted to address the difference in selection criteria. In this analysis (Fig. 3Go), the mean changes in hemoglobin level (adjusted for transfusions and stratified by most common doses) were higher for all groups relative to the original analysis. Thus, no difference in the relative effect on change in hemoglobin level was observed when the epoetin alfa and darbepoetin alfa patients were placed on equal footing with respect to baseline hemoglobin selection criteria.



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  		Figure 3. Sensitivity analysis for mean change in hemoglobin level: subset of patients with baseline hemoglobin levels ≤10.5 g/dl. Mean (95% CI) changes in hemoglobin level at weeks 5 and 8 are shown for the subset of patients with baseline hemoglobin levels ≤10.5 g/dl in each of the most common starting dose groups (darbepoetin alfa, 100 µg QW; darbepoetin alfa, 200 µg Q2W; and epoetin alfa, 40,000 U QW). Intent-to-treat analysis; missing values and values within 28 days after transfusion were imputed by carrying the last nonmissing or pretransfusion value forward.

 

   DISCUSSION
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 Additional Reading
 
Prospective clinical trials are an essential tool for evaluating drug effects and conducting definitive comparisons in an environment of minimal bias; however, retrospective chart reviews can also provide valuable information that complements data obtained in clinical trials. For example, the eligibility restrictions in a clinical trial result in a more narrow patient population being evaluated. In addition, adherence to a strict protocol for dosing may not reflect real-world drug utilization. In contrast, chart review studies provide the opportunity to evaluate drug usage patterns and outcomes in the setting of clinical practice and in a more diverse patient population. Retrospective studies are, therefore, an important aspect of clinical research, as the results assist practitioners in making formulary decisions, establishing and evaluating treatment guidelines, and evaluating the actual costs of treatment. As few published data are available to describe the real-world community practice usage patterns and relative clinical effectiveness of erythropoietic agents, the results presented here provide insight for those currently evaluating these agents in their practices.

This retrospective observational cohort study was designed to evaluate the initial usage patterns and effectiveness of darbepoetin alfa compared with epoetin alfa after therapeutic substitution at a large, community-based oncology network. As per standard practice in the U.S., most (86%) epoetin alfa-treated patients included in the study received a starting dose of 40,000 U QW. Most (85%) darbepoetin-alfa-treated patients received a fixed starting dose of 100 µg QW or the equivalent weekly dose rate administered Q2W (200 µg). During the period of adoption of darbepoetin alfa in the Tennessee Oncology network following its approval, many physicians initially chose to administer this agent on a weekly schedule to ease the transition from weekly epoetin alfa dosing. At the present time, physicians in the network are generally administering darbepoetin alfa at a starting dose of 200 µg Q2W. Since the conversion to the 200 µg Q2W darbepoetin alfa dose, additional data from a single-arm community-based study have confirmed the effectiveness of the equivalent weight-based dose of 3 µg/kg and its comparability with standard doses of epoetin alfa [16, 17]. Additionally, a recent analysis suggests that response to a darbepoetin alfa fixed dose is not expected to differ from the weight-based dose [18].

Overall utilization of darbepoetin alfa and epoetin alfa were comparable in this comparison of chart reviews, with both erythropoietic agents associated with a generally similar frequency of dose increases. Clinical outcomes were also considered comparable for darbepoetin alfa and epoetin alfa. Both the incidence of transfusion and the volume of blood transfused were lower for the darbepoetin alfa group; however, this may be due, in part, to the slight imbalance in mean baseline hemoglobin levels (10.1 g/dl for the darbepoetin alfa group versus 9.6 g/dl for the epoetin alfa group). The mean change in hemoglobin level was also slightly lower for epoetin alfa than for either of the two darbepoetin alfa groups at both week 5 and week 8.

The sensitivity analysis, in which hemoglobin values due to transfusions were not excluded, indicated that the mean change in hemoglobin level was inflated relative to the primary analysis, particularly at week 5. If the transfusion rate is higher than reported here, as has been reported in some clinical trials (e.g., 28% [5] and 25% [6]), the inflation of the mean change in hemoglobin level due to the inclusion of transfusion hemoglobin values could be substantial. Thus, handling of transfusion hemoglobin values is an important aspect of analysis, particularly when making comparisons of results among different studies.

A comparison of equivalent QW and Q2W doses of darbepoetin alfa was made possible as a result of the initial use of a weekly darbepoetin alfa regimen by many physicians just after the approval of darbepoetin alfa. The darbepoetin alfa 100 µg QW and 200 µg Q2W dose groups had similar mean changes in hemoglobin level, indicating that extension of the darbepoetin alfa dosing interval had no effect on darbepoetin alfa dose efficiency, as previously reported in the clinical trial setting [11].

One of the potential limitations of this study is the difference in patient selection criteria between the two groups with respect to baseline hemoglobin criteria (patients in the epoetin alfa group were restricted to baseline hemoglobin levels ≤10.5 g/dl, whereas no restriction was made for the darbepoetin alfa group) and weeks of data required (5 weeks for epoetin alfa versus 8 weeks for darbepoetin alfa). The reason for these differences is rooted in the timing of the audits. At the time when the first audit was conducted, the primary concern was to evaluate usage of epoetin alfa in the network; thus, only 5 weeks of data were specified as a requirement for inclusion (although data were collected through 8 weeks when available). When the second audit was conducted, 8 weeks of data were specified as a requirement to allow evaluation of darbepoetin alfa efficacy over a longer period. Similarly, with respect to baseline hemoglobin requirements, the hemoglobin requirement was set at ≤10.5 g/dl in the first audit, which was considered an appropriate threshold for initiation of erythropoietic therapy at that time. However, more recently, practice has shifted to treatment initiation at higher hemoglobin levels, thus no hemoglobin limit was set in the second audit as long as the patient had a diagnosis of chemotherapy-induced anemia. These differences were addressed by sensitivity analyses, in which subset analyses were conducted to compensate for any imbalance in the groups caused by patient selection criteria. The sensitivity analyses support the findings of the principal analyses.

The noncontemporaneous timeframes for data collection also represent a limitation of the study, as data obtained from patients treated with epoetin alfa were collected approximately 2 years before data from patients treated with darbepoetin alfa were collected. We note that the dosing practices for epoetin alfa (starting dose of 40,000 U QW with a dose increase to 60,000 U) that were recorded in the chart audit in 2000 continue to reflect current practice.

There was a 0.5-g/dl difference in mean baseline hemoglobin levels between the two groups (9.6 g/dl for epoetin alfa and 10.1 g/dl for darbepoetin alfa). This difference would be expected to favor the epoetin alfa group for the change in hemoglobin level end point and the darbepoetin alfa group for the transfusion end points. However, when the darbepoetin 200 µg Q2W dose group and the epoetin alfa 40,000 U QW dose group, which had a more similar mean baseline hemoglobin value (9.9 g/dl versus 9.7 g/dl), were compared, the conclusion of comparable efficacy was unchanged. Further, a sensitivity analysis restricting the darbepoetin alfa group to the ≤10.5 g/dl baseline hemoglobin criterion used for the epoetin alfa data collection did not change the relative results. For these reasons, it is unlikely that differences in baseline hemoglobin level have biased interpretation of these results.


   CONCLUSION
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 Additional Reading
 
The results of this retrospective cohort study provide evidence that darbepoetin alfa, at doses of 100 µg QW or 200 µg Q2W, is at least as effective as epoetin alfa after 8 weeks of therapy for the treatment of chemotherapy-induced anemia in a community-based oncology setting. Comparable effectiveness for darbepoetin alfa 200 µg Q2W and epoetin alfa 40,000 U QW in patients with chemotherapy-induced anemia was recently confirmed in an independent retrospective cohort study [19]. The results of the darbepoetin alfa chart review also confirm that the dosing interval of darbepoetin alfa can be extended from 1 week to 2 weeks with no loss in dose efficacy. The ability to administer darbepoetin alfa less frequently and more flexibly than epoetin alfa provides an improvement in the management of chemotherapy-induced anemia for physicians and their staff, and enhances convenience for patients and caregivers.


   ACKNOWLEDGMENT
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 Additional Reading
 
The authors thank Wanda Krall, Ph.D., and James Ziobro for assistance with manuscript preparation and Michiel Hagendoorn for statistical programming. Jeffrey Patton and Timothy Reeves received research support from Amgen Inc. Joel Wallace is an employee of Amgen Inc.


   REFERENCES
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
Additional Reading
 

  1. Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 1999;91: 1616–1634.[Abstract/Free Full Text]
  2. Egrie JC, Dwyer E, Browne JK et al. Darbepoetin alfa has a longer circulating half-life and greater in vivo potency than recombinant human erythropoietin. Exp Hematol 2003;31:290–299.[CrossRef][Medline]
  3. Elliott S, Lorenzini T, Asher S et al. Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat Biotechnol 2003;21:414–421.[CrossRef][Medline]
  4. Aranesp® prescribing information. Thousand Oaks, CA: Amgen, Inc., 2002.
  5. Abels R. Erythropoietin for anaemia in cancer patients. Eur J Cancer 1993;29A(suppl 2):S2–S8.
  6. Littlewood TJ, Bajetta E, Nortier JW et al. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001;19:2865–2874.[Abstract/Free Full Text]
  7. Glaspy J, Bukowski R, Steinberg D et al. Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group. J Clin Oncol 1997;15:1218–1234.[Abstract/Free Full Text]
  8. Demetri GD, Kris M, Wade J et al. Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 1998;16:3412–3425.[Abstract]
  9. Gabrilove JL, Cleeland CS, Livingston RB et al. Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times-weekly dosing. J Clin Oncol 2001;19:2875–2882.[Abstract/Free Full Text]
  10. Shasha D, George MJ, Harrison LB. Once-weekly dosing of epoetin alfa increases hemoglobin and improves quality of life in anemic cancer patients receiving radiation therapy either concomitantly or sequentially with chemotherapy. Cancer 2003;98:1072–1079.[CrossRef][Medline]
  11. Glaspy JA, Jadeja JS, Justice G et al. Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer 2002;87:268–276.[CrossRef][Medline]
  12. Vansteenkiste J, Pirker R, Massuti B et al. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 2002;94:1211–1220.[Abstract/Free Full Text]
  13. Hedenus M, Hansen S, Taylor K et al. Randomized, dose-finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Br J Haematol 2002;119:79–86.[CrossRef][Medline]
  14. Kotasek D, Steger G, Faught W et al. Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy; results of a double-blind, placebo-controlled, randomised study. Eur J Cancer 2003;39:2026–2034.
  15. Kotasek D, Albertsson M, Mackey J et al. Once per cycle dosing of darbepoetin alfa is feasible in anemic cancer patients receiving chemotherapy. Ann Oncol 2002;13(suppl 5):170.[Abstract/Free Full Text]
  16. Vadhan-Raj S, Mirtsching B, Charu V et al. Assessment of hematologic effects and fatigue in cancer patients with chemotherapy-induced anemia given darbepoetin alfa every two weeks. J Support Oncol 2003;1:1–8.
  17. Mirtsching B, Charu V, Vadhan-Raj S et al. Every-2-week darbepoetin alfa is comparable to rHuEPO in treating chemotherapy-induced anemia. Results of a combined analysis. Oncology (Huntingt) 2002;16(suppl 11):31–36.
  18. Jumbe N, Yao B, Rovetti R et al. Clinical trial simulation of a 200-µg fixed dose of darbepoetin alfa in chemotherapy-induced anemia. Oncology (Huntingt) 2002;16(suppl 11):37–44.
  19. Schwartzberg L, Shiffman R, Tomita D et al. A multicenter retrospective cohort study of practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia. Clin Ther 2003;25:2781–2796.[CrossRef][Medline]

   ADDITIONAL READING
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 Additional Reading
 
Received November 3, 2003; accepted for publication February 20, 2004.




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Cost Analysis of Erythropoietic-Stimulating Therapy Dosing in Oncology Inpatients
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R. Adamson, I. Lew, P. Allen, A. Misuro, and P. Malacrida
Therapeutic interchange of darbepoetin alfa for epoetin alfa in a multiinstitution health care system
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R. Waltzman, C. Croot, G. R. Justice, M. R. Fesen, V. Charu, and D. Williams
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Darbepoetin versus epoetin
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L. Belayev, L. Khoutorova, W. Zhao, A. Vigdorchik, A. Belayev, R. Busto, E. Magal, and M. D. Ginsberg
Neuroprotective Effect of Darbepoetin Alfa, a Novel Recombinant Erythropoietic Protein, in Focal Cerebral Ischemia in Rats
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L. S. Schwartzberg, L. K. Yee, F. M. Senecal, V. Charu, D. Tomita, J. Wallace, and G. Rossi
A Randomized Comparison of Every-2-Week Darbepoetin Alfa and Weekly Epoetin Alfa for the Treatment of Chemotherapy-Induced Anemia in Patients With Breast, Lung, or Gynecologic Cancer
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