Objective. To determine the dose-conversion ratio (DCR) between epoetin alfa and darbepoetin alfa in cancer patients and compare the treatment costs of both agents at the estimated DCRs.
Methods. A comprehensive search of the literature was carried out on clinical trials evaluating patients with chemotherapy-related anemia treated with epoetin alfa or darbepoetin alfa. A multivariate meta-analysis regression was conducted to determine the relative doses of these two agents at which they were equally effective. The effectiveness measure used was the area under the hemoglobin change curve. Using the estimated DCR for each dosing regimen, therelativecostofepoetinalfa and darbepoetin alfa treatments in Canada was evaluated.
Results. Twenty-nine study arms, evaluating 12 923 patients (10 582 treated with epoetin alfa and 2341 treated with darbepoetin alfa), were eligible for this study. Results comparing specific dosing regimens indicated that the DCRs were systematically lower than 200:1. The cost premium associated with darbepoetin alfa weekly drug cost was between 37 and 44% above epoetin alfa for the same level of effectiveness.
Conclusion. Based on the evidence from this meta-analysis, epoetin alfa appeared to be more cost-effective compared to darbepoetin alfa in Canada for cancer patients.
Cella D.Factors influencing quality of life in cancer patients: anemia and fatigue . Semin Oncol1998; 25: 43-46 .
2.
Cella D , Dobrez D , Glaspy JA.Control of cancer-related anemia with erythropoietic agents: a review of evidence for improved quality of life and clinical outcomes . Ann Oncol2003; 14: 511-519 .
3.
Barnett A , Crémieux PY , Fendrick MA , et al.Anemia related costs for cancer patients . JMC Med2002; 6: 20-28 .
4.
Epoetin Alfa (EPREX®). Product package insert. Retrieved 23 August 2005, from http://www.janssen-ortho.com/JOI/pdf_files/Eprex_E.pdf
5.
Epoetin Alfa (PROCRIT®). Product package insert. Retrieved 23 August 2005, from http://www.procrit.com/common/prescribing_information/PROCRIT/PDF/ProcritBooklet.pdf
6.
Darbepoetin Alfa (Aranesp®). Product package insert. Retrieved 23 August 2005, from http://www.aranesp.com/pdf/aranesp_PI.pdf
7.
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 Oncol1998; 16: 3412-3425 .
8.
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 Oncol2001; 19: 2875-2882 .
9.
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 Inst2002; 94: 1211-1220 .
10.
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 Oncol2003; 1: 131-138 .
11.
Witzig TE , Silberstein PT , Loprinzi CL , et al.Phase III, randomized, double-blind study of epoetin alfa versus placebo in anemic patients with cancer undergoing chemotherapy . J Clin Oncol2004; 22: 1-12 .
12.
Chang J , Couture F , Young S , et al.Once weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy . J Clin Oncol2004; 23: 2597-2605 .
13.
Scott S.Dose conversion from recombinant human erythropoietin to darbepoetin alfa . Pharmacotherapy2002; 22: 160S-65S ; review.
14.
Rosberg JH , Ben-Hamadi R , Cremieux PY , et al.Dose conversion and cost effectiveness of erythropoietic therapies in chemotherapy-related anaemia . Clin Drug Invest2005; 25: 33-48 .
15.
Nissenson AR , Swan SK , Lindberg JS , et al.Randomized, controlled trial of Darbepoetin Alfa for the treatment of anemia in hemodialysis patients . Am J Kidney Dis2002; 40: 110-118 .
16.
Duh MS , Lefebvre P , Fastenau J , et al.Assessing the clinical benefits of erythropoietic agent using area under the hemoglobin change curve . Oncologist2005; 10: 438-448 .
17.
Pawlicki M , Jassem J , Bosze P , et al.A multicenter study of recombinant human erythropoietin (Epoetin alpha) in the management of anemia in cancer patients receiving chemotherapy . Anticancer Drugs1997; 8: 949-957 .
18.
Heatherington AC , Schuller J , Mercer AJ.Pharmacokinetics of novel erythropoiesis stimulation protein (NESP) in cancer patients: preliminary report . Br J Cancer2001; 84: 11-16 .
19.
Glapsy JA.The potential for anemia treatment to improve survival in cancer patients . Oncology (Williston Park)2002; 16: 35-40 ; review.
20.
Harousseau JL , Fumoleau P , Lange W , et al.Increasing hemoglobin levels with epoetin alfa anemic hematologic cancer patients receiving chemotherapy correlates significantly with improved quality of life . Presented at the Forty-Sixth Annual Meeting and Exposition of the American Society of Hematology, San Diego, CA, 2004; abstract.
21.
Shasha D , George MJ , Harrison LB.Once-weekly dosing of epoetin increases hemoglobin and improves quality of life in anemic cancer patients receiving radiation therapy either concomitantly or sequentially with chemotherapy . Cancer2003; 98: 1072-1079 .
22.
Dammacco F , Castoldi G , Rodjer S.Efficacy of Epoetin alpha in the treatment of anemia in multiple myeloma . Br J Haematol2001; 113: 172-179 .
23.
Demetri GD.Anemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy . Br J Cancer2001; 84: 31-37 .
24.
Quirt I , Robeson C , Lau CY , et al.Epoetin alfa therapy increases hemoglobin levels and improves quality of life in patients with cancer-related anemia who are not receiving chemotherapy and patients with anemia who are receiving chemotherapy . J Clin Oncol2001; 19: 4126-4134 .
25.
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 Oncol2001; 19: 2865-2874 .
26.
Hedenus M , Adriansson M , San Miguel J , et al.Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study . Br J Haematol2003; 122: 394-403 .
27.
Glaspy JA , Jadeja JS , Justice G , et al.A randomized, active-control, pilot trial of front-loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anemia during chemotherapy for malignant disease . Cancer2003; 97: 1312-1320 .
28.
Hedenus M , Hansen S , Taylor K , et al.Randomized, dose-finding study of Darbepoetin Alfa in anemic patients with lymphoproliferative malignancies . Br J Haematol2002; 119: 79-86 .
29.
Schwartzberg L , Yee L , Charu V , et al.Comparable efficacy and safety of darbepoetin alfa 200 mcg every 2 weeks (Q2W) and epoetin alfa 40 000 U weekly (QW) in patients (Pts) with breast cancer: results of a randomized comparison . Presented at the Twenty-Seventh Annual San Antonio Breast Cancer Symposium, San Antonio, TX, 2004; poster presentation.
30.
Glaspy J , Berg R , Tomita D , et al.Final results of a phase 3, randomized, open-label study of darbepoetin alfa 200 mcg every 2 weeks (Q2W) versus epoetin alfa 40 000 U weekly (QW) in patients with chemotherapy-induced anemia (CIA) . Forty-First Annual Meeting of the American Society for Clinical Oncology, Orlando, FL, 2005; abstract.
31.
Glaspy J , Bukowski R , Steinberg D , et al.Impact of therapy with epoetin alfa on clinical outcomes of patients with nonmyeloid malignancies during cancer chemotherapy in community practice . J Clin Oncol1997; 15: 1218-1234 .
32.
Granetto C , Ricci S , Martoni A , et al.Comparing the efficacy and safety of fixed versus weight-based dosing of epoetin alfa in anemic cancer patients receiving platinum-based chemotherapy . Oncol Rep2003; 10: 1289-1296 .
33.
Waltzman R , Croot C , Justice GR , et al.Randomized comparison of epoetin alfa (40 000 U weekly) and darbepoetin alfa (200 microg every 2 weeks) in anemic patients with cancer receiving chemotherapy . Oncologist2005; 10: 642-650 .
34.
Huber PJ.The behavior of maximum likelihood estimates under nonstandard conditions . In Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability, Volume 1. University of California Press, 1967: 221-223 .
35.
White H.A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity . Econometrica1980; 48: 817-830 .
36.
Moore D , McCabe GP.Introduction to the practice of statistics. WH Freeman & Co , 2002.
37.
DeGroot M.Probability and statistics. Addison-Wesley , 1986.
38.
Bassem I , Razzouk BI , Hockenberry M , et al.Influence of hemoglobin response to epoetin alfa on quality-of-life in anemic children with cancer receiving myelosuppressive chemotherapy . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
39.
Yilmaz D , Cetingul N , Kantar M , et al.A single institutional experience: is epoetin alpha effective in anemic children with cancer?Pediatr Hematol Oncol2004; 21: 1-8 .
40.
Charu V , Saidman B , Ben-Jacob A , et al.Improvements in fatigue are associated with early treatment with every- 3-week (Q3W) darbepoetin alfa (DA) treatment in anemic patients (pts) receiving chemotherapy (CTX) . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
41.
Messino M , McGary E , Williams D.Epoetin alfa 60 000 U SC QW induction followed by 60 000 U SC Q2W: final study results of a novel treatment strategy for chemotherapy-related anemia . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
42.
O’Shaughnessy JA , Vukelja SJ , Holmes FA , et al.Feasibility of quantifying the effects of epoetin alfa therapy on cognitive function in women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy . Clin Breast Cancer2005; 5: 439-446 .
43.
Rearden TP , Charu V , Saidman B , et al.Results of a randomized study of every three-week dosing (Q3W) of darbepoetin alfa for chemotherapy-induced anemia (CIA) . J Clin Oncol2004; 22: 14S-14S ; abstract.
44.
Libutti MPF.Darbepoetin a, quality of life and fatigue in outpatients in chemo-radiotherapy . J Clin Oncol2004; 22: 14S-14S ; abstract.
45.
Cleeland C , Crawford J , Lubeck D , et al.Using the MD Anderson Symptom Inventory (MDASI) to assess symptom burden and interference: Interim results of an open-label study of darbepoetin Alfa 200 mcg every 2 weeks (Q2W) for the treatment of chemotherapy-induced anemia (CIA) . J Clin Oncol2004; 22: 14S-14S ; abstract.
46.
Ariganello O , Mancuso A , Di Molfetta M , et al.A new induction schedule of epoetin alfa 40.000 IU in anemic patients with advanced lung cancer . Lung Cancer2004; 46: 119-124 .
47.
Cortesi E , Mancuso A , De Pasquale Ceratti A , et al.Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy . Oncologist2004; 9: 459-468 .
48.
Iconomou G , Koutras A , Rigopoulos A , et al.Effectof recombinant human erythropoietin on quality of life in cancer patients receiving chemotherapy: results of a randomized controlled trial . J Pain Symptom Manage2003; 25: 512-518 .
49.
Arslan M , Evrensel T , Kurt E , et al.Comparison of clinical outcomes of different erythropoietin usage strategies . Tumori2004; 90: 394-398 .
50.
Auerbach M , Ballard H , Trout JR , et al.Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial . J Clin Oncol2004; 22: 1301-1307 .
51.
Bindi M , Montemaggi P , Sabatino M , et al.Reticulocytes can represent an early indicator of the erythropoietic response to Darbepoetin alfa in the anemia by chemotherapy . J Clin Oncol2004; 22: 14S-14S ; abstract.
52.
Boccia RV , Lui D , Silberstein P , et al.An evaluation of the effectiveness of darbepoetin alfa 300 mcg every 3 weeks (Q3W) on clinical outcomes in cancer patients with chemotherapy-induced anemia . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
53.
Boccia RV , Liu D , Silberstein P , et al.Evaluating the effectiveness of darbepoetin alfa 300 mcg Q3W for the treatment of chemotherapy-induced anemia . Presented at the ASCO Annual Meeting, 2005; abstract.
54.
Canon J , Vansteenkiste J , Bodoky G , et al.Final results of a randomized, double-blind, active-controlled trial of darbepoetin alfa administered once every 3 weeks (Q3W) for the treatment of anemia in patients receiving multicycle chemotherapy . Presented at the ASCO Annual Meeting, 2005; abstract.
55.
Charu V , Belani CP , Gill AN , et al.A controlled, randomized, open-label study to evaluate the effect of every-2-week darbepoetin alfa for anemia of cancer . J Clin Oncol2004; 22: 14S-14S ; abstract.
56.
Coleman EA , Anaissie E , Coon SK , et al.A randomized trial of home-based exercise for patients receiving aggressive treatment and epoetin alfa for multiple myeloma: Hemoglobin (Hb), transfusion, fatigue and performance as outcomes . J Clin Oncol2004; 22: 14S-14S ; abstract.
57.
Marinaccio M , Mele E , Poma S , et al.Pretreatment normalization of mild anemia with epoetin alfa predicts long-term outcome for women with epithelial ovarian cancer . J Clin Oncol2004; 22: 14S-14S ; abstract.
58.
Muñoz-Langa J , Juan O , Olmos S , et al.Once-weekly dosing of epoetin alfa are similar to three-times-weekly dosing to improve hemoglobin levels in chemotherapy patients: results from multicenter prospective cohort study . Presented at the ASCO Annual Meeting, 2005; abstract.
59.
Savonije J , Van Groeningen C , Van Bochove A , et al.Early intervention with epoetin-alfa during platinum-based chemotherapy . J Clin Oncol2004; 22: 14S-14S ; abstract.
60.
Shasha D , Williams D.Epoetin alfa 40 000 U QW increases Hb and is safe in anemic patients with cancer not receiving chemotherapy or radiation therapy . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
61.
Shasha D , Henry DH , Williams D.Epoetin alfa (EPO) 60 000 U every 2 weeks (Q2W) in patients (pts) with cancer not receiving chemotherapy (CT) or radiotherapy (RT) . Presented at the ASCO Annual Meeting, 2005; abstract.
62.
Ben-Hamadi R , Duh MS , Henckler A , et al.Cost-effectiveness of once weekly epoetin alfa and darbepoetin alfa in treating chemotherapy-induced anemia . Presented at the ASCO Annual Meeting, 2005; abstract.
63.
Blayney D , Vadhan-Raj S , Tomita D , et al.Efficacy of darbepoetin alfa in chemotherapy-induced anemia in gastrointestinal cancers . Presented at the ASCO Annual Meeting, 2005; abstract.
64.
Dicato M , Vercammen E , Liu K , et al.The relationship of body weight and efficacy of fixed dose epoetin alfa vs placebo . Presented at the ASCO Annual Meeting, 2005; abstract.
65.
Fastenau J , Lefebvre P , Duh MS , et al.Evaluation of the relationship between early hemoglobin rise during epoetin alfa treatment and improved patient-reported quality of life . J Clin Oncol2004; 22: 14S-14S ; abstract.
66.
Littlewood TJ , Nortier J , Rapoport B , et al.Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non-platinum chemotherapy . Hematol Oncol2003; 21: 169-180 .
67.
McKenzie RS , Lefebvre P , Rosberg J , et al.Comparison of anemia outcomes associated with early response to epoetin alfa (EPO) with QW and TIW dosing . J Clin Oncol2004; 22: 14S-14S ; abstract.
68.
McKenzie SR , Duh MS , Lefevbre P , et al.Greater area under the hemoglobin change curve is associated with improved outcomes in elderly patients receiving epoetin alfa for chemotherapy-related anemia . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
69.
Nordyke R , Chang CH , Chiou CF , et al.Validation of a patient satisfaction questionnaire for anemia treatment (PSQ-An) . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
70.
Rosberg J , Cremieux PY , McKenzie SR , et al.Benefits of early hemoglobin response to epoetin alfa in elderly patients with chemotherapy-related anemia . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
71.
Sloan JA , Schaefer PL , Witzig TE , et al.Relationships among quality of life and survival in anemic patients with advanced cancer undergoing chemotherapy . Presented at the ASCO Annual Meeting, 2005; abstract.
72.
Gregory SA , Blayney DW , Vadhan-Raj S , et al.Efficacy of darbepoetin alfa in the treatment of chemotherapy-induced anemia in non-Hodgkin’s lymphoma . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
73.
Vadhan-Raj S , Mirtsching B , Gregory SA , et al.Baseline(BL) covariates of response to darbepoetin alfa (DA) every 2 weeks (Q2W) in patients (pts) with chemotherapy-induced anemia (CIA) . J Clin Oncol2004; 22: 14S-14S ; abstract.
74.
Vansteenkiste J , Tomita D , Rossi G , et al.Darbepoetin alfa in lung cancer patients on chemotherapy: a retrospective comparison of outcomes in patients with mild versus moderate-to-severe anaemia at baseline . Support Care Cancer2004; 12: 253-262 .
75.
Vercammen E , Ludwig H , Liu K , et al.Analysis of the effect of body weight on the efficacy and safety of epoetin alfa . Presented at the ASCO Annual Meeting, 2005; abstract.
76.
Waltzman R , Williams D.Head-to-head comparison of epoetin alfa (EPO) 40 000 U QW vs darbepoetin alfa (DARB) 200 mg Q2W in anemic cancer patients receiving chemotherapy (CT): final results of a planned interim analysis (IA) . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
77.
Baltz B , Gregory SA , Ehmann WC , et al.Initial dosing of epoetin alfa 60 000 U QW followed by Q2W maintenance for anemic patients with cancer receiving chemotherapy . J Clin Oncol2004; 22: 14S-14S ; abstract.
78.
Chang J , Phippard L , Sharma D , et al.A phase II randomized trial of three loading doses of epoetin alfa followed by every three-week (q3w) dosing in cancer patients receiving chemotherapy . Presented at the ASCO Annual Meeting, 2005; abstract.
79.
Cortesi E , Ricci S , Ucci G , et al.Randomized phase III study comparing standard TIW and weekly dosage of epoetin alfa with 2 weeks loading dose: preliminary results . Presented at the ASCO Annual Meeting, 2005; abstract.
80.
Grosbach A , Langer CJ , Montoya V , et al.Epoetin alfa 60 000 U QW followed by 80 000 U Q3W maintenance in patients with anemia and cancer receiving chemotherapy . J Clin Oncol2004; 22: 14S-14S ; abstract.
81.
Migliorino MR , De Petris L , Martelli O , Mancuso A , Salvia R , Marinis F.Hemoglobin increase in advanced/metastatic lung cancer patients receiving multicycle chemotherapy and weekly darbepoetin alfa: an initial ongoing experience . J Clin Oncol2004; 22: 14S-14S ; abstract.
82.
Hesketh PJ , Arena F , Patel D , et al.A randomized controlled trial of darbepoetin alfa administered as a fixed or weight-based dose using a front-loading schedule in patients with anemia who have nonmyeloid malignancies . Cancer2004; 100: 859-868 .
83.
Kotasek D , Canon J-L , San Miguel J , et al.Correction/maintenance dosing (front loading) of darbepoetin alfa: final results from a randomized phase 3 active controlled trial . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
84.
Montoya V , Williams D.Every-three-week (Q3W) maintenance dosing of epoetin alfa in anemic cancer patients receiving chemotherapy: 60 000 U SC QW to target Hb 12 g/dl, followed by 80 000 U SC Q3W . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
85.
Santini D , Vincenzi B , La Cesa A , et al.A new dose-intense epoetin alfa regimen effective in anemic cancer patients receiving chemotherapy: an open-label, non randomized, pilot study . Anticancer Res2005; 25: 669-674 .
86.
Spiriti MA , Latagliata R , Niscola P , et al.Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome . Ann Hematol2005; 84: 167-176 .
87.
Tarabay G , Braly P , Baker JJ , et al.Treatment of anemia with epoetin alfa 80 000 U QW in cancer patients receiving chemotherapy . J Clin Oncol2004; 22: 14S-14S ; abstract.
88.
Tarantolo S , Bouda DW.Early results from a novel treatment strategy for chemotherapy-related anemia: Epoetin alfa 60 000 U SC QW induction followed by 60 000 U SC Q2W . J Clin Oncol2004; 22: 14S-14S ; abstract.
89.
Waltzman RJ , Braly P , Williams D.Safety and efficacy of epoetin alfa initiated at 80 000 U once weekly in anemic cancer patients receiving chemotherapy . Presented at the ASH Annual Meeting and Exposition, 2004; abstract.
90.
Glaspy JA , Jadeja JS , Justice G , et al.Darbepoetin alfa given every 1 or 2 weeks alleviates anemia associated with cancer chemotherapy . Br J Cancer2002; 87: 268-276 .
