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Clinical impact of epoetins in the treatment of anemia with special emphasis on patients with lymphoid malignancies.: dosing, iron supplementation and safety
Umeå University, Faculty of Medicine, Radiation Sciences.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to determine the relevant dose of arbepoetin-alfa (DA) in patients with lymphoproliferative diseases (LPD) and chemotherapy induced anemia (CIA), to study the clinical impact of intravenous (IV) iron supplementation combined with epoetin beta treatment, to identify factors that might predict hemoglobin (Hb) response to treatment with epoetins and to investigate safety of DA.

A dose-finding phase II study was able to assess a reasonable DA dose of 2.25 μg/kg once weekly for the treatment of CIA in patients with LPD. Dose-response trends were observed for the different dose cohorts although not statistically significant for any of the endpoints. However a significantly higher proportion of patients achieved Hb response (increase ≥2 g/dL) in the combined DA groups than in placebo (P<0.001).

A larger pivotal phase II trial was performed in a similar setting o confirm that the dose 2.25μg/kg once weekly was appropriate and safe. The proportion of patients achieving Hb response was significantly higher in the DA group (60%) than in the placebo group (18%) (P<0,001) and resulted in higher mean changes in Hb than placebo from baseline, 2.66 g/dl versus 0.69 /dl. Also a significantly lower proportion of patients in the DA group (31%) received RBC tranfusions than in the placebo group (48%). The short-term safety of DA with the tested dose was confirmed. The efficacy of DA was consistent for all end points independent of malignancy type or baseline endogenous erythropoietin serum levels.

The correction of moderate anemia in truly iron repleted patients with clinically stable LPD not receiving hemotherapy or RBC transfusions with epoetin beta treatment, with or without IV iron treatment was studied in an open label randomized trial. Also the impact on iron kinetics was assessed. The mean change in Hb concentration from baseline to end of treatment (EOT ) was 2.91 versus 1.50 g/dL respectively (P<0.0001). There was a significant (P<0.0001) difference in mean Hb at EOT between the iron and no-iron groups (13.0 g/dL versus 11.8 g/dL). Hb response was achieved by significantly more patients in the iron group (P=0.0012)than in the no-iron group (93% versus 53%) and the median time to achieve a Hb response was 6 weeks in the iron group compared with 12 weeks in the no-iron group. The mean weekly epoetin dose per patient was statistically significant lower in the iron group at week 13 (P =0.029) and at least 25% lower at EOT.

To investigate the long-term safety of DA in cancer patients with CIA four previously published double blind, randomized placebo-controlled phase II -III studies were analysed (n = 1.129). Median durations of progression-free survival and overall survival was comparable between DA and placebo for lung cancer (median follow up 15.8 months), for LPD (median follow up 32.6 months) and in the pooled population (follow up 4 months).

Place, publisher, year, edition, pages
Umeå: Strålningsvetenskaper , 2007. , 58 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1069
Keyword [en]
anemia, cancer, lymphoproliferative malignancies, erythropoietin, intravenous iron, safety
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-1024ISBN: 91-7264-214-9 (print)OAI: oai:DiVA.org:umu-1024DiVA: diva2:139995
Public defence
2007-03-16, 244, Lionssalen, 7, Norrlands universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2007-02-22 Created: 2007-02-22 Last updated: 2009-05-19Bibliographically approved
List of papers
1. Randomized dose-finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies
Open this publication in new window or tab >>Randomized dose-finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies
Show others...
2002 (English)In: British Journal of Haematology, ISSN 0007-1048, Vol. 119, no 1, 79-86 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2146 (URN)
Available from: 2007-02-22 Created: 2007-02-22Bibliographically approved
2. Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study
Open this publication in new window or tab >>Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study
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2003 (English)In: British Journal of Haematology, ISSN 0007-1048, Vol. 122, no 3, 394-403 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2147 (URN)
Available from: 2007-02-22 Created: 2007-02-22Bibliographically approved
3. Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study.
Open this publication in new window or tab >>Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study.
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2007 (English)In: Leukemia, ISSN 0887-6924, Vol. 21, no 4, 627-632 p.Article in journal (Refereed) Published
Keyword
anemia, cancer, erythropoietin, intravenous iron, lymphoproliferative malignancies
Identifiers
urn:nbn:se:umu:diva-12258 (URN)doi:10.1038/sj.leu.2404562 (DOI)17252006 (PubMedID)
Available from: 2007-03-28 Created: 2007-03-28Bibliographically approved
4. Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials
Open this publication in new window or tab >>Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials
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2005 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, Vol. 23, no 28, 6941-6948 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-14364 (URN)doi:10.1200/jco.2005.03.434 (DOI)16192582 (PubMedID)
Available from: 2006-11-09 Created: 2006-11-09Bibliographically approved

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