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Randomized Comparison of Epoetin Alfa (40,000 U Weekly) and Darbepoetin Alfa (200 µg Every 2 Weeks) in Anemic Patients with Cancer Receiving Chemotherapy

^a St. Vincent’s Comprehensive Cancer Center, New York, New York, USA; ^b North Mississippi Hematology and Oncology Associates, Tupelo, Mississippi, USA; ^c Pacific Coast Hematology/Oncology Medical Group, Fountain Valley, California, USA; ^d Hutchinson Clinic, Hutchinson, Kansas, USA; ^e Pacific Cancer Medical Center, Anaheim, California, USA; ^f Ortho Biotech Clinical Affairs, LLC, Bridgewater, New Jersey, USA

Correspondence: Roger Waltzman, M.D., Saint Vincent’s Comprehensive Cancer Center, 325 West 15th Street, New York, New York 10011, USA. Telephone: 212-604-6058; Fax: 212-604-6038; e-mail: rwaltzman{at}aptiumoncology.com

	ABSTRACT

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This is the first randomized, open-label, multicenter trial designed and powered to directly compare the hemoglobin (Hb) response to epoetin alfa (EPO), 40,000 U once weekly (QW), with that to darbepoetin alfa (DARB), 200 µ g every 2 weeks (Q2W), in anemic patients with cancer receiving chemotherapy (CT). Transfusion requirements, quality of life (QOL), and safety also were evaluated. Adults with solid tumors scheduled to receive CT for 12 weeks and with baseline Hb 11 g/dl were randomized to receive either EPO 40,000 U QW (n = 178) or DARB 200 µg Q2W (n = 180) s.c. for up to 16 weeks. Doses were increased for nonresponders (Hb increase <1 g/dl) after 4 (EPO) or 6 (DARB) weeks, as per National Comprehensive Cancer Network guidelines, and were reduced for a rapid rise in Hb (>1.3 g/dl [EPO] or >1.0 g/dl [DARB] within any 2-week period) or for an Hb level >13 g/dl. The proportion of patients achieving a 1-g/dl Hb rise by week 5, the primary end point, was significantly higher with EPO (47.0%) than with DARB (32.5%), and EPO-treated patients achieved a 1-g/dl Hb increase significantly earlier than those receiving DARB (median, 35 days versus 46 days). The mean increase in Hb from baseline was significantly higher at weeks 5, 9, 13, and the end of the study with EPO than with DARB. The number of units transfused per patient was significantly lower for the EPO group than for the DARB group. The proportions of patients requiring transfusions, mean QOL improvements, and tolerability profiles were similar in the two groups.

Key Words. Epoetin alfa • Darbepoetin alfa • Cancer • Anemia • Transfusions • Randomized trial

	INTRODUCTION

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Chemotherapy-induced anemia has debilitating effects on patients with cancer [1–4]. Epoetin alfa (Procrit^®; Ortho Biotech Products, L.P., Raritan, NJ, http://www.orthobiotech.com) and darbepoetin alfa (Aranesp^®; Amgen Inc., Thousand Oaks, CA, http://www.amgen.com) are growth factors that stimulate RBC formation and are approved and widely adopted for the management of chemotherapy-induced anemia.

A large body of clinical evidence exists showing that epoetin alfa, a recombinant human erythropoietin, administered 3 times a week or once weekly (QW), is well tolerated and highly effective at increasing hemoglobin (Hb) and decreasing transfusion requirements in anemic patients with cancer [5–9]. The successful treatment of anemia with epoetin alfa in this patient population has been shown to correlate with measurable and clinically beneficial increases in energy level, functional status, and quality of life (QOL) [9–12].

Darbepoetin alfa is a constitutively different erythropoietic protein that is hyperglycosylated, increasing its serum half-life but lowering its binding affinity. Nevertheless, studies suggest that, in patients with cancer receiving chemotherapy, the serum half-lives of epoetin alfa and darbepoetin alfa are similar (40 hours and 33–50 hours, respectively) [13–16]. Though molecularly distinct from epoetin alfa, darbepoetin alfa binds to the same erythropoietin receptor and stimulates erythropoiesis by the same mechanism [17]. Clinical trials in anemic patients with cancer receiving chemotherapy have demonstrated that darbepoetin alfa also is effective at raising Hb levels and reducing transfusion requirements [18–21].

The dosages of epoetin alfa (40,000 U QW) and darbepoetin alfa (200 µg once every 2 weeks [Q2W]) used in this trial have been evaluated in clinical trials [21, 22] and are consistent with those most commonly used in clinical practice and with recommendations from published guidelines [8, 23] regarding the use of these agents.

Retrospective studies evaluating the relative efficacy and safety of these two erythropoiesis-stimulating agents have been published [24–26]. Unlike previous trials, this prospective trial was specifically designed and powered a priori with a primary end point of statistically comparing the hematologic responses of the two agents.

The primary efficacy end point was the percentage of patients demonstrating an increase in Hb of 1 g/dl by week 5 of therapy. Patients with chemotherapy-induced anemia exhibiting an earlier Hb response have been shown to have better outcomes, including a greater likelihood of a meaningful Hb response (Hb increase >2 g/dl), greater QOL improvements, reductions in transfusions, and lower doses of erythropoietic therapy than patients showing either a later or no response [27].

	MATERIALS AND METHODS

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The protocol was approved by the investigational review board of the 55 participating U.S. clinical sites, and all patients gave written informed consent.

Study Population
Eligible patients were anemic (Hb 11 g/dl) men and women (18 years of age) with a solid tumor malignancy scheduled to receive cyclic chemotherapy for at least 12 weeks; with a life expectancy of at least 6 months; with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2; and with adequate renal, hepatic, and hematologic functions (not the result of transfusion).

Patients were excluded if they had received any erythropoietic agent within 3 months, had anemia due to factors other than cancer or chemotherapy, had received more than two prior chemotherapy regimens, or if radiation therapy was included in their treatment plans. Also excluded were patients with a history of stem cell or bone marrow transplant; untreated brain metastases; uncontrolled hypertension; poorly controlled seizures; known hypersensitivity to mammalian cell–derived products or human albumin; transfusion of packed red blood cells (PRBCs) within 28 days; any unstable medical condition; or a history of uncontrolled cardiac arrhythmias, pulmonary embolism, or thrombosis within the previous 6 months.

Study Design
The study was designed as a prospective, multicenter, randomized, open-label comparison of the efficacies of epoetin alfa and darbepoetin alfa. The effects of these agents on transfusion requirements, QOL, and safety also were evaluated. All patients underwent an initial screening period within 10 days before the first dose of study treatment, during which baseline information, including demographics and clinical laboratory data (hematology, clinical chemistry, iron profile, and serum antierythropoietin antibody at select sites), was collected and participant eligibility was assessed. Hb, hematocrit (Hct), and QOL were measured within 3 days before the first dose of study drug.

Eligible patients were randomized 1:1 to receive either epoetin alfa (starting dose, 40,000 U s.c. QW) or darbepoetin alfa (starting dose, 200 µg s.c. Q2W).

Randomization was stratified by study site and chemotherapy type (platinum- or nonplatinum-based). The study drugs were sponsor-supplied in prepackaged kits for each patient. Epoetin alfa was provided as commercially available Procrit^® and darbepoetin alfa was provided as commercially available Aranesp^®. The initial study drug administration occurred on day 1 of week 1 and was required to coincide with day 1 of the chemotherapy cycle to minimize early variability in the timing of erythropoietic growth factor administration and response with respect to the chemotherapy cycle [16]. Study treatment was administered for up to 16 weeks. Dose escalation for nonresponders (Hb increase <1 g/dl) occurred based on recommendations of the National Comprehensive Cancer Network [23] and the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) guidelines [8] after 4 weeks (epoetin alfa dose increased to 60,000 U QW) or 6 weeks (darbepoetin alfa dose increased to 300 µg Q2W) of treatment. Study drug was withheld if Hb was >13 g/dl and was resumed at a 25% dose reduction when Hb was 12 g/dl. A similar dose reduction was required for rapid Hb response (>1.3 g/dl in a 2-week period for epoetin alfa patients or >1.0 g/dl for darbepoetin alfa patients), as per the respective package inserts at the time of study initiation.

An oral supplement of ferrous sulfate, 325 mg, or an equivalent commercially available iron supplement, was to be taken by each patient daily throughout the study, if tolerated and not contraindicated. If not tolerated, an i.v. formulation of iron could have been prescribed.

Hb, Hct, and blood pressure were monitored weekly, before administration of study drug. Specifically, with regard to the primary end point, Hb was measured at week 5 before dose escalation. Patients were evaluated monthly (CBC, blood pressure, body weight, transfusion use, changes in chemotherapy, and adverse events [AEs]) for up to 16 weeks on treatment and followed for safety thereafter. Clinical laboratory and ECOG performance status evaluations were done at the study completion. Patients were withdrawn if chemotherapy was discontinued before 12 weeks on therapy or changed from a platinum- to a nonplatinum-based regimen or vice versa.

QOL was assessed using the Functional Assessment of Cancer Therapy–Anemia Fatigue subscale and the Energy Level and Ability to Perform Daily Activities subscales of the 100-mm Linear Analogue Scale Assessment [28], the results of which have been shown to significantly correlate with Hb level in patients with cancer receiving chemotherapy [29, 30].

End Points
The primary efficacy end point was the Hb response rate, which is the proportion of patients in each group achieving an Hb increase of 1 g/dl by week 5 (i.e., within 4 weeks of treatment) not attributable to a PRBC or whole blood transfusion. Secondary end points included the proportion of patients achieving at least a 1- or 2-g/dl increase in Hb at week 9 or at the study end, time to response, change in Hb from baseline at weekly intervals, transfusion requirements, and mean changes in the three measured QOL sub-scales. Safety was assessed by laboratory tests, vital sign measurements, physical examinations, and the incidence and severity of AEs.

Statistical Analysis
Based on the outcomes of previous studies [19, 31], a sample size of 300 (150 per treatment group) was estimated to yield a 90% power to detect a statistically significant treatment difference in the proportion of patients achieving an Hb response by week 5 (epoetin alfa minus darbepoetin alfa), assuming a type I error rate 0.0125 (one-sided).

The analysis of the primary efficacy end point was based on the first 300 patients to complete 4 weeks of study treatment. The proportions of patients achieving an Hb response by week 5 in the two treatment groups were compared using a logistic regression model with the stratification factor of chemotherapy type. The overall significance level for this analysis was 0.0125, one-sided. The protocol had a provision for an adaptation procedure to increase enrollment to 400 participants should the interim analysis prove inconclusive [32].

Analyses of secondary efficacy end points were based on all patients who received at least one dose of a study drug and had at least one postbaseline Hb value or transfusion (modified intent-to-treat population [mITT]). Hb values obtained within 28 days following a PRBC transfusion were set to missing for all efficacy analyses. Hb data post-transfusion as well as any missing Hb data were analyzed using a last-value-carried-forward (LVCF) method. All secondary efficacy end points were tested at a significance level of 0.05, two-sided.

The time to an Hb increase of 1 g/dl was analyzed by Kaplan-Meier estimates and a Cox regression model with treatment group and chemotherapy type as effects and baseline Hb value as a covariate. The analysis method used for the primary efficacy end point was also performed on the proportion of patients achieving a 1-g/dl or 2-g/dl increase in Hb by week 9 and at the end of the study, and on the proportion of patients receiving a PRBC transfusion from week 5 to the end of the study. An analysis of covariance (ANCOVA) model with treatment group as the fixed effect and baseline Hb as the covariate was used to compare the treatment group difference in the number of PRBC units transfused per transfused patient from week 5 to the end of the study, and was used to compare the treatment group difference in the change from baseline in Hb at each visit.

The changes from baseline in QOL at week 5, week 9, and the end of the study were analyzed by treatment group. A correlation analysis assessed the relationship between changes in Hb and changes in the QOL variables. Patients receiving at least one dose of a study drug were included in the safety analysis. All statistical analyses were done using the SAS statistical software (version 8.2; SAS Institute, Cary, NC, http://www.sas.com).

	RESULTS

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Study Population
Three hundred fifty-eight patients were enrolled and randomized to receive epoetin alfa (n = 178) or darbepoetin alfa (n = 180); of these, 352 (175 epoetin alfa, 177 darbepoetin alfa) were in the mITT population (Fig. 1). Baseline characteristics for all randomized patients were similar in the two treatment groups (Table 1). Lung and breast cancer were the most common tumor types. At study entry, the majority of patients presented with tumor stage IV (including IVA or IVB), representing slightly more than one half of the patients in the epoetin alfa group (n = 101, 57%) and in the darbepoetin alfa group (n = 101, 56%). Stage II and III tumors were the next most common stages in both arms (Table 1). A higher percentage of patients received nonplatinum-based chemotherapy.

View larger version (19K): [in this window] [in a new window]   Figure 1. Consolidated Standards of Reporting Trials diagram. aReasons for early discontinuation: 30 as a result of an adverse event or disease progression; 24 at the request of the sponsor, primarily because of protocol deviations; 21 at the investigator’s or patient’s request, primarily as a result of discontinuation of chemotherapy or protocol deviation; 19 after a change from a nonplatinum-based to a platinum-based chemotherapy (or vice versa); 12 because of death; two lost to follow-up; and 40 for other reasons (e.g., delay, discontinuation, or completion of chemotherapy before 12 weeks on study; protocol deviation). Abbreviation: mITT, modified intent-to-treat.

The mean cumulative doses of the study drugs were 418,479.9 U for epoetin alfa patients (n = 178) and 1,178.4 µg for darbepoetin alfa patients (n = 180), and the mean durations of treatment were similar in the two groups (77.0 and 79.5 days, respectively). The percentages of patients who had their dose increased, to 60,000 U QW epoetin alfa at week 5 (33%) or to 300 µg Q2W darbepoetin alfa at week 7 (34%), were similar, as were the percentages of patients in the epoetin alfa and darbepoetin alfa groups who had any dose increase (44% and 41%, respectively) or dose reduction (42% and 31%, respectively).

Efficacy Evaluations
The analysis of the primary efficacy end point was based on data from the first 305 patients to complete 4 weeks of study treatment (five patients completed on the same day).

Hb Response by Week 5
The percentages of patients who achieved an Hb increase 1 g/dl by week 5 of treatment, not attributable to PRBC transfusion, were 47.0% in the epoetin alfa group (71/151) and 32.5% in the darbepoetin alfa group (50/154) (Fig. 2). These findings were statistically significant in favor of epoetin alfa (p = .0078, one-sided). When summarized by chemotherapy type, 36% and 25% of epoetin alfa and darbepoetin alfa patients, respectively (platinum group), and 54% and 38% of epoetin alfa and darbepoetin alfa patients, respectively (non-platinum group), achieved an Hb increase 1 g/dl by week 5.

View larger version (11K): [in this window] [in a new window]   Figure 2. Percentage of responders at week 5 (modified intent-to-treat population; last value carried forward). Patients were required to have completed 4 weeks on study to be evaluable for response.

Time to Hb Response
The Kaplan-Meier estimates of the median time to an Hb rise of 1 g/dl were 35.0 days (epoetin alfa) and 46.0 days (darbepoetin alfa) (p = .0057, log-rank test). This finding was supported by results of the Cox regression hazard ratio (1.40) that indicated patients receiving epoetin alfa achieved an Hb response 40% earlier than those treated with darbepoetin alfa (p = .0081).

Change in Hb
The weekly changes in Hb from baseline for the epoetin alfa and darbepoetin alfa groups are shown in Figure 3.

View larger version (13K): [in this window] [in a new window]   Figure 3. Change in hemoglobin (Hb) level from baseline over study period (modified intent-to-treat population).

Transfusion Requirement
For patients on study and at risk for transfusion between week 5 and the end of the study, 20/155 (12.9%) patients in the epoetin alfa group and 29/163 (17.8%) patients in the darbepoetin alfa group received at least one PRBC transfusion (p = .2936). Monthly transfusion rates for PRBCs and/or whole blood in the epoetin alfa treatment group ranged from 8.6% (month 1) to 4.8% (month 4) and were consistently lower than those seen in the darbepoetin alfa group (11.3% at month 1 to 7.4% at month 4) with the largest difference seen for month 2 (7.1% for epoetin alfa, 14.1% for darbepoetin alfa). The mean number of PRBC units received per transfused patient from week 5 to the study end was significantly lower for the epoetin alfa group (2.5 units; range, 1–6) than for the darbepoetin alfa group (3.9 units; range, 2–10; p = .0334) as well as over the course of the entire study (post hoc analysis). The total absolute numbers of PRBC units transfused on study treatment were 81 in the epoetin alfa group and 156 in the darbepoetin alfa group.

QOL Evaluations
Mean improvements from baseline to week 9 and the end of the study were observed for the three QOL assessments for patients receiving epoetin alfa and those receiving darbepoetin, and a positive correlation between the changes in QOL scores and Hb level was observed.

Safety Evaluations
The safety population included 178 patients who received epoetin alfa and 180 patients who received darbepoetin alfa. The incidences and patterns of AEs were similar, and were generally those expected for patients with cancer receiving chemotherapy. Most (98%) were judged by the investigators to be unrelated to the study treatment. The AEs reported most frequently for epoetin alfa and darbepoetin alfa, respectively, were neutropenia (17% and 26%), nausea (33% and 27%), and diarrhea (26% and 20%). A similar number of patients in each treatment group (n = 15, 8%) were withdrawn following an AE, and most AEs were related to the patient’s underlying cancer or chemotherapy.

Predefined clinically significant thrombotic vascular events were reported for 20 (11%) patients in the epoetin alfa group and 17 (9%) patients in the darbepoetin alfa group (Table 3).

Fifty-nine patients (epoetin alfa, 25; darbepoetin alfa, 34) had an AE that led to death, all considered to be unrelated to study treatment.

Little variation was seen in vital sign measurements or routine physical examination findings in either treatment group. With the exception of larger increases in RBCs and Hb in the epoetin alfa group, there were no differences between the groups in the mean values of the hematology or serum chemistry parameters. No patient in either group tested positive for serum antierythropoietin antibodies.

	DISCUSSION

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Results of this prospective, randomized trial in anemic patients with solid tumors receiving chemotherapy demonstrate a hematologic response rate by week 5 that was statistically superior for epoetin alfa (40,000 U s.c. QW) compared with darbepoetin alfa (200 µg s.c. Q2W) and was apparent before dose increases for an inadequate response were allowed in either treatment group. In addition, patients treated with QW epoetin alfa had significantly greater increases in weekly Hb from week 3 to the study end. The Hb responses for epoetin alfa at week 5 and at the study end were similar to results previously observed for epoetin alfa 40,000 U QW (47%–66%; [9], data on file). Weekly Hb results have not been previously reported for darbepoetin alfa 200 µg Q2W, so this study provides the first published account of the weekly Hb performance for this regimen throughout the duration of treatment. There did not appear to be convincing evidence that baseline iron status or iron supplementation was a confounding variable in results for the primary end point of response rate in this study.

Analyses of previous data showed that an early Hb response was associated with significantly better clinical outcomes [27]. Separate exploratory analyses for this study were done [33] and confirmed that early Hb response is an appropriate measure to evaluate treatment effects. Also, because the average treatment duration for erythropoietic therapies has been shown to be approximately 8–10 weeks [34, 35], an earlier response to treatment is desirable.

Most previously published comparisons of epoetin alfa and darbepoetin alfa have been retrospective pooled analyses of previously conducted studies [24–26]. Such investigations introduce the potential for confounding biases because of differences in study design, patient populations, and statistical methodologies, and also for reporting bias, because they are not designed nor powered to make statistical comparisons.

Recently, Schwartzberg and colleagues reported the results of a pooled analysis of three randomized prospective trials comparing epoetin alfa (40,000 U QW) with darbepoetin alfa (200 µg Q2W) in patients with chemotherapy-induced anemia [36]. The trials were designed to validate a specific QOL tool. The authors’ conclusion that the two agents achieved comparable hematologic outcomes was based on selected secondary study assessments. Conversely, the present study was designed and powered as a superiority trial to directly compare the hematologic responses of epoetin alfa and darbepoetin alfa.

Although there was a significant difference in favor of epoetin alfa for mean units transfused per transfused patient (transfusion intensity) in this study, the overall percentage of patients who required at least one PRBC transfusion between week 5 and the study end (transfusion frequency) and the corresponding monthly transfusion rate were only numerically lower for epoetin alfa than for darbepoetin alfa (no statistical significance).

QW epoetin alfa and Q2W darbepoetin alfa provided similar improvements in QOL, perhaps because both treatments were active in raising Hb levels. Both agents also demonstrated similar safety profiles.

	CONCLUSIONS

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Epoetin alfa and darbepoetin alfa are widely prescribed for the management of chemotherapy-induced anemia. This adequately powered, randomized comparison of response rates of weekly s.c. administration of epoetin alfa (40,000 U) and darbepoetin alfa (200 µg) given Q2W in patients with chemotherapy-induced anemia demonstrated an earlier hematologic response for epoetin alfa. Transfusion intensity, but not transfusion frequency, also was significantly lower for epoetin alfa.

	APPENDIX

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Investigator list. Alabama: Susan M. Ferguson, M.D., Allen L. Yeilding, M.D., Birmingham; Luis F. Pineda, M.D., Hoover. Arkansas: Carroll Scroggin, Jr., M.D., Jonesboro. California: Veena Charu, M.D., Anaheim; Haresh S. Jhangiani, M.D., Glen R. Justice, M.D., Fountain Valley; Peter Eisenberg, M.D., Greenbrae; N. Simon Tchekmedyian, M.D., Long Beach; Syed Jilani, M.D., Redondo Beach; Prasad R. Dighe, M.D., Stockton; Peter P. Yu, M.D., Sunnyvale. Colorado: Mark Hancock, M.D., Michael McLaughlin, M.D., Denver. Delaware: Michael J. Guarino, M.D., Newark. Florida: Craig W. Englund, M.D., Inverness; Yousif Abubakr, M.D., Jacksonville; Michael J. Kelley, M.D., Ph.D., Ormond Beach; Ranjith B. Dissanayake, M.D., Allen Patton, M.D., Pensacola. Georgia: Frederick M. Schnell, M.D., F.A.C.P., Macon. Hawaii: Brian Issell, M.D., Honolulu. Illinois: Joyce Samuel, M.D., Chicago. Kansas: Mark R. Fesen, M.D., Hutchinson. Kentucky: John T. Hamm, M.D., Louisville. Louisiana: Harry McGaw, M.D., Houma. Maryland: Young Joo Lee, M.D., Stephen Noga, M.D., David Andrew Riseberg, M.D., Baltimore. Massachusetts: Reed Drews, M.D., Boston. Mississippi: Christopher C. Croot, M.D., Tupelo. Missouri: Patrick L. Gomez, M.D., Springfield. New Jersey: Michael A. Schleider, M.D., Englewood; Stanley Waintraub, M.D., Hackensack. New Mexico: Timothy M. Lopez, M.D., Santa Fe. New York: Barry H. Kaplan, M.D., Ph.D., Fresh Meadows; James T. D’Olimpio, M.D., Manhasset; Paolo A. Paciucci, M.D., New York City; Seetha R. Murukutla, M.D., Staten Island. North Carolina: Jennifer L. Garst, M.D., Durham; Glenn Lesser, M.D., Winston-Salem. North Dakota: Louis Geeraerts, M.D., Fargo. Ohio: Leslie R. Laufman, M.D., Columbus. Oklahoma: Howard Ozer, M.D., Oklahoma City. Oregon: Mark U. Rarick, M.D., Portland. South Carolina: George Geils, Jr., M.D., Charleston. Texas: David H. Gordon, M.D., Garry H. Schwartz, M.D., San Antonio. Virginia: Forrest Swan, Jr., M.D., Abingdon; Attique Samdani, M.D., Richmond; Paul D. Richards, M.D., Salem; Masoom Kandahari, M.D., Woodbridge. Washington: David E. McCune, M.D., Tacoma; Rakesh Gaur, M.D., Vancouver. Wisconsin: Tarit K. Banerjee, M.D., Marshfield.

	DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

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Dr. Waltzman is a consultant for, owns stock in, and receives support from Ortho Biotech/Johnson & Johnson. Dr. Charu owns stock in Pacific Cancer Medical Center. Dr. Williams owns stock in Johnson & Johnson and is an employee of Ortho Biotech Clinical Affairs, LLC.

	AUTHORS' NOTE

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Results of this study were presented at the 2005 ASCO Annual Meeting (abstract 8030), the 2004 ASCO Annual Meeting (abstract 8153), the 2004 ASH Annual Meeting (abstract 4233), and the 2003 ASH Annual Meeting (abstract 4391).

	ACKNOWLEDGMENT

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We wish to acknowledge Patricia Matone of Scientific Information Services for writing contributions and PPD Development for site monitoring, data management, statistics, and programming.

This is study PR02-27-047, sponsored by Ortho Biotech Clinical Affairs, L.L.C.

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	ADDITIONAL READING

Top Abstract Introduction Materials and methods Results Discussion Conclusions Appendix Disclosure of potential... Authors' note References Additional reading

Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 2000;92:497.[Free Full Text]

Henry DH. Epoetin alfa for the treatment of cancer- and chemotherapy-related anaemia: product review and update. Expert Opin Pharmacother 2005;6:295–310.[Medline]

Witzig TE, Silberstein PT, Loprinzi CL et al. Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol 2005;23:2606–2617.

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