Enhancement of platelet recovery after myelosuppressive chemotherapy by recombinant human megakaryocyte growth and development factor in patients with advanced cancer

Purpose: To explore the influence of dose and schedule on the ability of pe gylated 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 c ancer were randomized to receive PEG-rHuMGDF subcutaneously at different do ses and durations before administration of carboplatin 600 mg/m(2), cycloph osphamide 1,200 mg/m(2), and filgrastim 5 mu g/kg/d. PEG-rHuMGDF was not gi ven after the first cycle of chemotherapy but was given after the second an d subsequent cycles. Chemotherapy was given every 28 days for up to six cyc les. Results: In patients who received the same dose of chemotherapy for at leas t two cycles, the platelet nadir war significantly higher (47.5 x 10(9)/L v 35.5 x 10(9)/L; P = .003) and duration of grade 3 or 4 thrombocytopenia si gnificantly shorter (0 v 3 days; P = .004) when PEG-rHuMGDF was administere d after chemotherapy. There was no evidence of an effect of PEG-rHuMGDF whe n it was given before chemotherapy. Platelet recovery after the first cycle of chemotherapy was no different for different PEG-rHuMGDF regimens, and t here was no difference between patients treated with PEG-rHuMGDF and histor ical controls treated with identical chemotherapy. There was a modest dose- related increase in progenitor cell levels after administration of PEG-rHuM GDF alone. peak levels of PBPC occurred later in cycle 2 than in cycle 1 bu t were not different in magnitude. Conclusion: PEG-rHuMGDF abrogated severe thrombocytopenia after dose-intens ive chemotherapy. However, it had only a modest effect on progenitor cell l evels and did not enhance progenitor cell mobilization after chemotherapy a nd filgrastim. J Clin Oncol 18:2852-2861. (C) 2000 by American Society of C linical Oncology.