Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy

Purpose: To explore the use of SD/01 (a polyethylene glycol-conjugated filg rastim shown in preclinical studies to have a prolonged half-life) in patie nts with chemotherapy-induced neutropenia. Patients and Methods: Thirteen patients with nonsmall-cell lung cancer were randomized to receive daily filgrastim (5 mu g/kg/d) or a single injection of SD/01 (30, 100, or 300 mu g/kg) 2 weeks before chemotherapy and again 2 4 hours after administration of carboplatin and paclitaxel. Pharmacodynamic , pharmacokinetic, and safety analyses were performed. Results: Peak serum concentrations of SD/01 and the duration of increased s erum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia . Prechemotherapy median absolute neutrophil counts (ANCs) in patients rece iving SD/01 were increased in a dose-dependent fashion, with the duration o f this effect also being dose dependent. After chemotherapy, median ANC nad irs were similar in the filgrastim cohort and the cohort receiving SD/01 30 mu g/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 mu g/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobil ized in all cohorts. Conclusion: A single dose of SD/01 increases the serum concentration of SD/ 01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobiliza tion are comparable or greater than those achieved with daily filgrastim. T he self-regulation of this molecule provides a potential therapeutic advant age in a variety of clinical settings associated with neutropenia. J Clin O ncol 18:2522-2528. (C) 2000 by American Society of Clinical Oncology.