Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer.
BACKGROUND
Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocyte colony formation and platelet production. It is likely to be useful in the management of severe thrombocytopenia. To determine its clinical activity and safety, we gave it to patients with advanced cancer before chemotherapy.


METHODS
Patients were randomly assigned to receive either PEG-rHuMGDF or placebo in a three to one ratio. PEG-rHuMGDF was given at a dose of 0.03, 0.1, 0.3, or 1.0 microgram/kg body weight. The study drug or placebo were administered daily by subcutaneous injection for up to 10 days or until a target platelet count was reached.


RESULTS
17 patients, median age 59 years, received either PEG-rHuMGDF (13 patients) or placebo (four patients). PEG-rHuMGDF produced a dose-dependent increase in platelet counts. Patients given placebo. 0.03, and 0.1 microgram/kg of PEG-rHuMGDF had median increases in platelet counts of 16%, 12%, and 39%. Those receiving 0.3 and 1.0 microgram/kg of PEG-rHuMGDF had an increase in blood platelets of between 51% and 584%. Platelets rose from day 6 of PEG-rHuMGDF administration and continued to rise after stopping the drug. The platelet count peaked between days 12 and 18 and remained above 450 x 10(9)/L for up to 21 days. There were no alterations in white-blood-cell count or haematocrit, and low toxicity. Platelets taken from patients during PEG-rHuMGDF administration and at the time of peak platelet count were morphologically and functionally normal.


CONCLUSIONS
The potency with which PEG-rHuMGDF stimulates platelet production and its low toxicity indicate that this is likely to be a useful agent for the management of thrombocytopenia.
Basser
R L
RL
Centre for Developmental Cancer Therapeutics, Parkville, Victoria Australia.
Rasko
J E
JE
Clarke
K
K
Cebon
J
J
Green
M D
MD
Hussein
S
S
Alt
C
C
Menchaca
D
D
Tomita
D
D
Marty
J
J
Fox
R M
RM
Begley
C G
CG
D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000097:blood*; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000209:etiology / Q000628:therapy*; D013926:Thrombopoietin / Q000008:administration & dosage / Q000627:therapeutic use*
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; C082218:MPL protein, human; D011092:Polyethylene Glycols; D013926:Thrombopoietin