Pharmacokinetic, Pharmacodynamic and Covariate Analysis of Subcutaneous Versus Intravenous Administration of Bortezomib
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ORIGINAL RESEARCH ARTICLE
Pharmacokinetic, Pharmacodynamic and Covariate Analysis of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients with Relapsed Multiple Myeloma Philippe Moreau • Ievgenii I. Karamanesht • Natalia Domnikova • Maryna Y. Kyselyova • Kateryna V. Vilchevska • Vadim A. Doronin • Alexander Schmidt • Cyrille Hulin • Xavier Leleu • Dixie-Lee Esseltine • Karthik Venkatakrishnan • Donna Skee • Huaibao Feng • Suzette Girgis • Andrew Cakana • Helgi van de Velde • William Deraedt • Thierry Facon Published online: 25 September 2012 Ó Springer International Publishing Switzerland 2012
Abstract Background and Objectives The proteasome inhibitor bortezomib is approved for the treatment of multiple myeloma (MM) and, in the US, for the treatment of mantle cell lymphoma following at least one prior therapy; the recommended dose and schedule is 1.3 mg/m2 on days 1, 4, 8 and 11 of 21-day cycles, and the approved routes of administration in the US prescribing information are by intravenous and, following a recent update, subcutaneous injection. Findings from a phase III study demonstrated that subcutaneous administration of bortezomib, using the same dose and schedule, resulted in similar efficacy with
an improved systemic safety profile (including significantly lower rates of peripheral neuropathy) versus intravenous bortezomib in patients with relapsed MM. The objectives of this report were to present a comprehensive analysis of the pharmacokinetics and pharmacodynamics of subcutaneous versus intravenous bortezomib, and to evaluate the impact of the subcutaneous administration site, subcutaneous injection concentration and demographic characteristics on bortezomib pharmacokinetics and pharmacodynamics. Patients and Methods Data were analysed from the pharmacokinetic substudy of the randomized phase III MMY3021 study and the phase I CAN-1004 study of subcutaneous
P. Moreau (&) University Hospital, 44093 Nantes cedex 01, France e-mail: [email protected]
C. Hulin Centre Hospitalier Universitaire Nancy, Nancy, France
I. I. Karamanesht Kiev BMT Centre, Kiev, Ukraine N. Domnikova Hematology Department, State Novosibirsk Regional Clinical Hospital, Novosibirsk, Russia M. Y. Kyselyova Crimean Republic Clinical Oncology Dispensary, Haematology Department, Simferopol, Ukraine K. V. Vilchevska Hematology Department, V.K. Gusak Institute of Urgent and Recovery Surgery, Academy of Medical Science, Donetsk, Ukraine V. A. Doronin City Clinical Hospital #40, Hematology Department, Moscow, Russia A. Schmidt Russian Research Institute of Hematology and Transfusiology, St Petersburg, Russia
X. Leleu T. Facon Hoˆpital Claude Huriez, Centre Hospitalier Re´gional Universitaire de Lille, Lille, France D.-L. Esseltine K. Venkatakrishnan Millennium Pharmaceuticals, Inc., Cambridge, MA, USA D. Skee H. Feng Janssen Research & Development, Raritan, NJ, USA S. Girgis Janssen Research & Development, Titusville, NJ, USA A. Cakana Janssen Research & Development, High Wycombe, Buckinghamshire, UK H. va
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