Justification for a Fixed Dose of Eflapegrastim, a Long-Acting G-CSF, in Patients Receiving Docetaxel-Cyclophosphamide Chemotherapy.
Justification for a Fixed Dose of Eflapegrastim, a Long-Acting G-CSF, in Patients Receiving Docetaxel-Cyclophosphamide Chemotherapy.
J Clin Pharmacol. 2020 Aug 21;:
Authors: Barrett JA, Greene D, Lakshmikanthan S, Kolli P, Chawla S, Lebel F
Abstract
Eflapegrastim (Rolontis) is a long-acting granulocyte colony-stimulating factor (G-CSF) produced by conjugating a human G-CSF analogue and a human immunoglobulin G4 Fc fragment, linked via a polyethylene glycol linker. Weight-based doses of 45 to 270 μg/kg eflapegrastim (12.3-73.6 μg/kg as G-CSF) were evaluated in a phase 2 study in patients. Based on these results, a fixed dose of 13.2 mg eflapegrastim (3.6 mg G-CSF) was compared with pegfilgrastim (6 mg G-CSF) in 2 phase 3 studies and in a pharmacokinetic single-arm multicenter study. Absolute neutrophil count (ANC) data from these 3 studies were evaluated in patients with early-stage breast cancer who were treated with docetaxel and cyclophosphamide (n = 669). Serum concentrations of eflapegrastim were determined by enzyme-linked immunosorbent assay. Eflapegrastim systemic exposures were higher in cycle 1 than in cycle 3, likely attributable to the higher ANC in cycle 3, increasing neutrophil-mediated clearance. Eflapegrastim elicited a greater effect on ANC than pegfilgrastim in patients at ∼60% of the G-CSF dose. Body weight had no clinically significant effect on response, justifying administration of a fixed dose of efla...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Barrett JA, Greene D, Lakshmikanthan S, Kolli P, Chawla S, Lebel F Tags: J Clin Pharmacol Source Type: research
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