THROMBOPOIETIC EFFECTS OF PEGYLATED RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR (PEG-RHUMGDF) IN PATIENTS WITH ADVANCED CANCER

Background Pegytated recombinant human megakaryocyte growth and develo pment factor (PEG-rHuMGDF) is a potent stimulator of megakaryocyte col ony formation and platelet production. It is likely to be useful in th e management of severe thrombocytopenia, To determine its clinical act ivity and safety, we gave it to patients with advanced cancer before c hemotherapy. 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 I.0 mu g/kg body weight. The study dr ug or placebo were administered daily by subcutaneous injection for up to 10 days or until a target platelet count was reached. Findings 17 patients, median age 59 years, received either PEG-rHuMGDF (13 patient s) or placebo (four patients), PEG-rHuMGDF produced a dose-dependent i ncrease in platelet counts. Patients given placebo, 0.03, and 0.1 mu g /kg of PEG-rHuMGDF had median increases in platelet counts of 16%, 12% , and 39%. Those receiving 0.3 and 1.0 mu g/kg of PEG-rHuMGDF had an i ncrease in blood platelets of between 51% and 584%. Platelets rose fro m day 6 of PEG-rHuMGDF administration and continued to rise after stop ping the drug. The platelet count peaked between days 12 and 18 and re mained above 450x10(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. I nterpretation The potency with which PEG-rHuMGDF stimulates platelet p roduction and its low toxicity indicate that this is likely to be a us eful agent for the management of thrombocytopenia.