Randomized, dose‐finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies

British Journal of Haematology - Tập 119 Số 1 - Trang 79-86 - 2002
Michael Hedenus1, Søren Hansen2, Kerry Taylor3, Chris Arthur4, Bertold Emmerich5, Claire Dewey6, David I. Watson6, Gregory Rossi7, Anders Österborg8
1Medical Department, Sundsvall Hospital, Sundsvall,
2Department of Internal Medicine, Hogland Hospital, Eksjö, Sweden,
3Mater Misericordiae Adult Hospital, Queensland,
4Haematology Department, Royal North Shore Hospital, St. Leonards, Australia
5Medizinische Klinik – Innenstadt, Abteilung Hâmatology und Onkologie, Klinikum der Universität München, Germany,
6Amgen Ltd, Cambridge, UK
7Amgen Inc., Thousand Oaks, CA, USA, and
8Departments of Haematology and Oncology, Karolinska Hospital, Stockholm, Sweden

Tóm tắt

Summary. Darbepoetin alfa is a novel erythropoiesis‐stimulating protein with a prolonged serum half‐life. This randomized, double‐blind, placebo‐controlled, dose‐finding study investigated the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies who were receiving chemotherapy. Patients were randomized in a 1:2:2:1 ratio to receive darbepoetin alfa 1·0 μg/kg (n = 11), 2·25 μg/kg (n = 22), 4·5 μg/kg (n = 22) or placebo (n = 11), administered subcutaneously once weekly for 12 weeks. No dose increases were allowed during the study. A higher proportion of patients achieved a haemoglobin response (defined as a ≥ 2·0 g/dl increase from baseline) in the darbepoetin alfa 1·0 μg/kg (45%), 2·25 μg/kg (55%) and 4·5 μg/kg (62%) groups than in the placebo group (10%; P < 0·01). The mean change in haemoglobin from baseline to week 13 was 1·56 g/dl in the 1·0 μg/kg group, 1·64 g/dl in the 2·25 μg/kg group and 2·46 g/dl in the 4·5 μg/kg group, compared with a mean change of 1·00 g/dl in the placebo group. The overall safety profile of darbepoetin alfa in this study was similar to that of placebo. These results show that darbepoetin alfa effectively and safely increased haemoglobin concentrations in patients with lymphoproliferative malignancies. Confirmative studies at doses of 2·25 and/or 4·5 μg/kg/week in this population are warranted.

Từ khóa


Tài liệu tham khảo

Abels R.I., 1992, Use of recombinant human erythropoietin in the treatment of anemia in patients who have cancer, Seminars in Oncology, 19, 29

10.1002/stem.5530110203

Beguin Y., 1998, Prediction of response to treatment with recombinant human erythropoietin in anemia associated with cancer, Medical Oncology, 15, 38

Casadevall N., 1998, Update on the role of epoetin alfa in hematologic malignancies and myelodysplastic syndromes, Seminars in Oncology, 25, 12

10.1182/blood.V86.12.4446.bloodjournal86124446

Cazzola M., 1996, Prediction of response to recombinant human erythropoietin (rHuEPO) in anemia of malignancy, Haematologica, 81, 434

Coiffier B., 2000, The impact and management of anaemia in haematological malignancies, Medical Oncology, 17, 2

10.1007/s005990050032

10.1046/j.1365-2141.2001.02715.x

10.1200/JCO.1998.16.10.3412

Draper N.R., 1981, Applied Regression Analysis, 266

10.1054/bjoc.2001.1746

10.1182/blood.V79.8.1987.1987

10.1200/JCO.2001.19.11.2875

Garton J.P., 1995, Epoetin alfa for the treatment of the anemia of multiple myeloma. A prospective, randomized, placebo‐controlled, double‐blind trial, Archives of Internal Medicine, 155, 2069, 10.1001/archinte.1995.00430190059008

10.1200/JCO.1997.15.3.1218

Glaspy J., 2000, Novel erythropoiesis stimulating protein (NESP) exhibits a prolonged serum half‐life (t1/2) in oncology patients (pts), Proceedings of ASCO, 19, 54a

Glaspy J., 2001, Randomized, active‐controlled, phase 1/2, dose‐escalation study of NESP administered weekly and every 2 weeks in patients with solid tumors, Proceedings of ASCO, 20, 387a

10.1093/jnci/91.19.1616

10.1054/bjoc.2001.1747

Kotasek D., 2000, Randomized, double‐blind, placebo‐controlled, phase I/II dose finding study of ARANESP™ administered once every 3 weeks in solid tumor patients, Blood, 96, 1268

10.1200/JCO.2001.19.11.2865

10.1056/NEJM199006143222402

10.1002/stem.5530110502

10.1182/blood.V84.4.1056.1056

Macdougall I.C., 2000, Novel erythropoiesis stimulating protein, Seminars in Nephrology, 20, 375

Macdougall I.C., 1999, Pharmacokinetics of novel erythropoiesis stimulating protein compared with Epoetin alfa in dialysis patients, Journal of the American Society of Nephrology, 10, 2392, 10.1681/ASN.V10112392

10.1159/000203625

10.1016/S0889-8588(05)70342-7

10.1007/BF02821932

Österborg A., 2000, The role of recombinant human erythropoietin in the management of anemic cancer patients: focus on haematological malignancies, Medical Oncology, 17, 17

Österborg A., 1996, Recombinant human erythropoietin in transfusion‐dependent anemic patients with multiple myeloma and non‐Hodgkin's lymphoma – a randomized multicenter study, Blood, 87, 2675, 10.1182/blood.V87.7.2675.bloodjournal8772675

Österborg A. Brandberg Y. Molostova V. Iosava G. Abdulkadyrov K. Hedenus M.&Messinger D.for the Epoetin Beta Hematology Study Group (2002)Randomized double‐blind placebo‐controlled trial of recombinant human erythropoietin epoetin beta in hematolic malignancies.Journal of Clinical Oncology 20 2486–2494.

Pirker R., 2001, A phase 3, double‐blind, placebo‐controlled, randomized study of novel erythropoiesis stimulating protein (NESP) in patients undergoing platinum treatment for lung cancer, Proceedings of ASCO, 20, 394a

10.1007/BF01696618

Thông tin
Thông tin xuất bản

British Journal of Haematology

Tập 119 Số 1

79-86

Thông tin tác giả