Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients

Purpose: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. Patients and Methods: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part 11) chemotherapy either a single-dose injection of Ro 25-8315 (20 mug/kg, n = 9; 60 mug/kg, n 9; 100 mug/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 mug/kg/d; part II, 5 mug/kg/d) (control group, n = 8). Results: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 mug/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L. by day +15. In part 11, high levels of circulating CD34+ cells (> 20 cells/muL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 mug/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. Conclusion: A single injection of Ro 25-8315 100 mug/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 mug/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 258315 should be determined according to the planned chemotherapy regimen. (C) 2001 by American Society of Clinical Oncology.