title: Prospective comparison of subcutaneous versus intravenous administration of bortezomib in patients with multiple myeloma.
abstract: This phase I study compared pharmacokinetics and pharmacodynamics, and assessed safety and efficacy of intravenous and subcutaneous administration of bortezomib. Relapsed or refractory multiple myeloma patients were randomized to receive bortezomib by standard intravenous bolus (n=12) or subcutaneous injection (n=12) at the recommended dose and schedule (1.3 mg/m2, days 1, 4, 8, 11; eight 21-day cycles). Plasma bortezomib concentration and percent 20S proteasome inhibition were measured at multiple time points on days 1 and 11, cycle 1. Systemic bortezomib exposure was similar between arms. As expected, mean maximum plasma concentration was lower and took longer to reach following subcutaneous administration. Overall 20S proteasome inhibition was similar between arms. Safety profile and response rate for the subcutaneous arm did not appear inferior to the intravenous arm, with good local tolerance of subcutaneous injection. Based on these exploratory findings, subcutaneous administration offers an alternative option to intravenous injection (ClinicalTrials.gov identifier: NCT00291538).
authors.affiliation: Department of Hematology, University Hospital, Nantes, France. philippe.moreau@chu-nantes.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Valerie
authors.initials: V
authors.lastname: Coiteux
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Milin
authors.initials: M
authors.lastname: Acharya
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau