Purpose: To explore the influence of dose and schedule on the ability of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) to abrogate thrombocytopenia after multiple cycles of chemotherapy and to mobilize peripheral-blood progenitor cells (PBPC). Patients and Methods: In this open-label study, 68 patients with advanced cancer were randomized to receive PEG-rHuMGDF subcutaneously at different doses and durations before administration of carboplatin 600 mg/m2, cyclophosphamide 1,200 mg/m2, and filgrastim 5 μg/kg/d. PEG-rHuMGDF was not given after the first cycle of chemotherapy but was given after the second and subsequent cycles. Chemotherapy was given every 28 days for up to six cycles. Results: In patients who received the some dose of chemotherapy for at least two cycles, the platelet nadir was significantly higher (47.5 x 109/L v 35.5 x 109/L; P = .003) and duration of grade 3 or 4 thrombocytopenia significantly shorter (0 v 3 days; P = .004) when PeG-rHuMGDF was administered after chemotherapy. There was no evidence of an effect of PEG-rHuMGDF when it was given before chemotherapy. Platelet recovery after the first cycle of chemotherapy was no different for different PEG-rHuMGDF regimens, and there was no difference between patients treated with PEG-rHuMGDF and historical controls treated with identical chemotherapy. There was a modest dose-related increase in progenitor cell levels after administration of PEG-rHuMGDF alone. Peak levels of PBPC ocurred later in cycle 2 than in cycle 1 but were not different in magnitude. Conclusion: PEG-rHMGDF abrogated severe thrombocylopenia afar dose-intensive chemotherapy. However, it had only a modest effect on progenitor cell levels and did not enhance progenitor cell mobilization after chemotherapy and filgrastim. (C) 2000 by American Society of Clinical Oncology.