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Randomized, Dose-Escalation Study of SD/01 Compared With Daily Filgrastim in Patients Receiving Chemotherapy

From the Thoracic Oncology Program, Duke Comprehensive Cancer Center, Durham, NC, and Amgen, Inc, Thousand Oaks, CA.

Address reprint requests to Jeffrey Crawford, MD, Duke University Medical School, Box 3198, Durham, NC 27710; email crawf006@ mc.duke.edu.

PURPOSE: To explore the use of SD/01 (a polyethylene glycol–conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia.

PATIENTS AND METHODS: Thirteen patients with non–small-cell lung cancer were randomized to receive daily filgrastim (5 µg/kg/d) or a single injection of SD/01 (30, 100, or 300 µg/kg) 2 weeks before chemotherapy and again 24 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 serum 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 receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 µg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 µg/kg. Dose-limiting toxicities were not noted. CD34⁺ cells were mobilized 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 mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.

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