Before Chemotherapy

The stimulatory effects of PEG-rHuMGDF and rHuTPO on megakaryocyte and platelet production have been suggested in several clinical trials in patients before

Fig. 11. PEG-rHuMGDF increases the platelet count in healthy humans. Healthy platelet apheresis donors were treated with a single dose of placebo (black bars), 1 pg/kg (white bars), or 3 pg/kg (gray bars) of PEG-rHuMGDF on d 1, and the platelet response was measured. There was no effect on the red or white cell count. (Reproduced with permission from ref. 100.)

Fig. 11. PEG-rHuMGDF increases the platelet count in healthy humans. Healthy platelet apheresis donors were treated with a single dose of placebo (black bars), 1 pg/kg (white bars), or 3 pg/kg (gray bars) of PEG-rHuMGDF on d 1, and the platelet response was measured. There was no effect on the red or white cell count. (Reproduced with permission from ref. 100.)

chemotherapy. When administered before chemotherapy as a daily subcutaneous injection, PEG-rHuMGDF produced a dose-dependent increase in peripheral blood platelet counts and a modest increase in megakaryocyte, erythroid, and myeloid progenitor cell counts in patients with advanced cancer (106-110). No evidence of platelet activation or altered platelet function was observed with PEG-rHuMGDF administration (111). rHuTPO has produced a dose-dependent increase in platelet counts in patients with sarcomas and gynecologic malignancies (112-116). A phase 1-2 study examined the effect of rHuTPO on megakaryocyte and platelet production before chemotherapy with doxorubicin and ifosfamide in patients with sarcomas who were at high risk of developing chemotherapy-induced thrombocytopenia. When given intravenously before chemotherapy, a single dose of rHuTPO was associated with a dose-dependent increase in peripheral platelets that began on d 4 and peaked on d 12 in most patients (113). This increase in platelet number was accompanied by a fourfold increase in bone marrow megakaryocytes and a marked expansion and mobilization of erythroid, myeloid, and megakaryocyte progenitor cells. A second trial investigated the clinical safety and activity of rHuTPO administered subcutaneously to previously treated patients with gynecologic malignancies before chemotherapy with carboplatin (116). As observed in the previous study, administration of a single subcutaneous dose of rHuTPO before chemotherapy produced a modest dose-dependent increase in circulating platelet counts.

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