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Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments

Journal article published in 2013 by Jennifer L. Pauley, John C. Panetta ORCID, Kristine R. Crews, Deqing Pei, Cheng Cheng, John McCormick, Scott C. Howard, John T. Sandlund, Sima Jeha, Raul Ribeiro, Jeffrey Rubnitz ORCID, Ching-Hon Pui, William E. Evans, Mary V. Relling
This paper is available in a repository.
This paper is available in a repository.

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Abstract

Purpose : It is advantageous to individualize high-dose methotrexate (HDMTX) to maintain adequate exposure while minimizing toxicities. Previously, we accomplished this through within-course dose adjustments. ; Methods : In this study, we evaluated a strategy to individualize HDMTX based on clearance of each individual’s previous course of HDMTX in 485 patients with newly diagnosed acute lymphoblastic leukemia. Doses were individualized to achieve a steady-state plasma concentration (Cpss) of 33 or 65 μM (approximately 2.5 or 5 g/m2/day) for low- and standard-/high-risk patients, respectively. ; Results : Individualized doses resulted in 70 and 63 % of courses being within 20 % of the targeted Cpss in the low- and standard-/high-risk arms, respectively, compared to 60 % (p