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Randomized, blinded, placebo-controlled phase I trial of pegylated
recombinant human megakaryocyte growth and development factor with
filgrastim after dose-intensive chemotherapy in patients with advanced
cancer
RL Basser, JE Rasko, K Clarke, J Cebon, MD Green, AP Grigg, J Zalcberg, B Cohen, J O'Byrne, DM Menchaca, RM Fox and CG Begley
Centre for Developmental Cancer Therapeutics, Parkville, Victoria,
Australia.
Thrombocytopenia caused by chemotherapy is an important cause of morbidity
and mortality in the treatment of malignant disease. Recombinant human
megakaryocyte growth and development factor (PEG- rHuMGDF) is a potent
stimulator of megakaryocytopoiesis and prevents chemotherapy-induced
thrombocytopenia in preclinical studies. We administered PEG-rHuMGDF with
filgrastim after dose-intensive chemotherapy to 41 patients with advanced
cancers to determine its safety and effects on hematologic recovery.
Carboplatin 600 mg/m2 and cyclophosphamide 1,200 mg/m2 were administered to
patients with advanced cancer. Patients were randomly assigned to receive
blinded study drug, either PEG-rHuMGDF or placebo (3-to-1 ratio),
commencing the day after chemotherapy. PEG-rHuMGDF was given at doses of
0.03, 0.1, 0.3, 1.0, 3.0, and 5.0 microg per kilogram body weight by daily
subcutaneous injection for between 7 and 20 days. All patients received
concurrent filgrastim 5 microg per kilogram body weight per day until
neutrophil recovery. Fifteen patients had received PEG-rHuMGDF alone in a
previous phase I study. Platelet function and peripheral blood progenitor
cells (PBPC) were assessed. PEG-rHuMGDF enhanced platelet recovery in a
dose-related manner when compared with placebo. The platelet nadir occurred
earlier in patients given PEG-rHuMGDF (P = .002) but there was no
difference in the depth of the nadir. Recovery to baseline platelet count
was achieved significantly earlier following PEG-rHuMGDF administration
compared with placebo (median, 17 days for PEG-rHuMGDF 0.3 to 5.0 microg/kg
versus 22 days for placebo, P = .014). In addition, platelet recovery was
faster in patients who had previously received PEG-rHuMGDF, suggesting that
pretreatment might be beneficial. Platelet function did not change during
or after administration of PEG-rHuMGDF. Levels of PBPC on day 15 after
chemotherapy were significantly greater in patients administered PEG-
rHuMGDF 0.3 to 5.0 microg/kg and filgrastim compared with those given
placebo plus filgrastim. PEG-rHuMGDF was well tolerated at all doses. Two
patients given PEG-rHuMGDF had a thrombotic episode. PEG-rHuMGDF
accelerates platelet recovery after moderately dose-intensive carboplatin
and cyclophosphamide, and is likely to be clinically useful in treatment of
chemotherapy-induced thrombocytopenia. Because it enhances mobilization of
PBPC by filgrastim, PEG-rHuMGDF might also allow more efficient collection
of stem cells for autologous or allogeneic transplantation.
Volume 89,
Issue 9,
pp. 3118-3128,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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D. J. Kuter and C. G. Begley
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November 15, 2002;
100(10):
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Thrombopoietin as a Drug: Biologic Expectations, Clinical Realities, and Future Directions
Clinical and Applied Thrombosis/Hemostasis,
July 1, 2002;
8(3):
193 - 212.
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|
|
|
|
|
|
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S. Nomura, K. Dan, T. Hotta, K. Fujimura, and Y. Ikeda
Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura
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|
|
|
|
|
|
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Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor
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April 1, 2002;
99(7):
2599 - 2602.
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|
|
|
|
|
|
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Thrombocytopenia caused by the development of antibodies to thrombopoietin
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December 1, 2001;
98(12):
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|
|
|
|
|
|
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Thrombopoietin therapy increases platelet yields in healthy platelet donors
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98(5):
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|
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|
|
|
|
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|
|
|
|
|
|
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132(5):
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|
|
|
|
|
|
|
E. Archimbaud, O. G. Ottmann, J. A. L. Yin, K. Lechner, H. Dombret, M. A. Sanz, G. Heil, P. Fenaux, W. Brugger, A. Barge, et al.
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94(11):
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[Abstract]
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|
|
|
|
|
|
|
M. De Serres, B. Ellis, J. E. Dillberger, S. K. Rudolph, J. T. Hutchins, C. M. Boytos, D. L. Weigl, and R. B. DePrince
Immunogenicity of Thrombopoietin Mimetic Peptide GW395058 in BALB/c Mice and New Zealand White Rabbits: Evaluation of the Potential for Thrombopoietin Neutralizing Antibody Production in Man
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|
|
|
|
|
|
|
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93(9):
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[Full Text]
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|
|
|
|
|
|
|
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April 15, 1999;
93(8):
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[Abstract]
[Full Text]
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|
|
|
|
|
|
|
T. Watanabe, Y. Kawano, S. Kanamaru, T. Onishi, S. Kaneko, Y. Wakata, R. Nakagawa, A. Makimoto, Y. Kuroda, Y. Takaue, et al.
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Blood,
February 15, 1999;
93(4):
1157 - 1163.
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[Full Text]
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|
|
|
|
|
|
|
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Multicycle High-Dose Chemotherapy and Filgrastim-Mobilized Peripheral-Blood Progenitor Cells in Women With High-Risk Stage II or III Breast Cancer: Five-Year Follow-Up
J. Clin. Oncol.,
January 1, 1999;
17(1):
82 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nakamura, C. F. Toombs, I. G. Duarte, R. S. Ronson, L. S. Schmarkey, S. L. Katzmark, J. Robinson, D. L. Dillehay, J. Vinten-Johansen, and R. A. Guyton
Recombinant human megakaryocyte growth and development factor attenuates postbypass thrombocytopenia
Ann. Thorac. Surg.,
October 1, 1998;
66(4):
1216 - 1223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kaushansky
Thrombopoietin
N. Engl. J. Med.,
September 10, 1998;
339(11):
746 - 754.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Neelis, T. P. Visser, W. Dimjati, G. R. Thomas, P. J. Fielder, D. Bloedow, D. L. Eaton, and G. Wagemaker
A Single Dose of Thrombopoietin Shortly After Myelosuppressive Total Body Irradiation Prevents Pancytopenia in Mice by Promoting Short-Term Multilineage Spleen-Repopulating Cells at the Transient Expense of Bone Marrow-Repopulating Cells
Blood,
September 1, 1998;
92(5):
1586 - 1597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.G. Begley, R. Basser, R. Mansfield, B. Thomson, W.R.L. Parker, J. Layton, B. To, J. Cebon, W.P. Sheridan, R.M. Fox, et al.
Enhanced Levels and Enhanced Clonogenic Capacity of Blood Progenitor Cells Following Administration of Stem Cell Factor Plus Granulocyte Colony-Stimulating Factor to Humans
Blood,
November 1, 1997;
90(9):
3378 - 3389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. X. Qian, S. m. Lee, Y. Suen, E. Knoppel, C. van de Ven, and M. S. Cairo
Decreased Interleukin-15 From Activated Cord Versus Adult Peripheral Blood Mononuclear Cells and the Effect of Interleukin-15 in Upregulating Antitumor Immune Activity and Cytokine Production in Cord Blood
Blood,
October 15, 1997;
90(8):
3106 - 3117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Abraham and R. L. Basser
Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies
Oncologist,
October 1, 1997;
2(5):
311 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
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