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Pauley JL, Panetta JC, Crews KR, et al. Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments. Cancer Chemother Pharmacol. 2013;72(2):369-78doi: 10.1007/s00280-013-2206-x.
Pauley, J. L., Panetta, J. C., Crews, K. R., Pei, D., Cheng, C., McCormick, J., Howard, S. C., Sandlund, J. T., Jeha, S., Ribeiro, R., Rubnitz, J., Pui, C. H., Evans, W. E., & Relling, M. V. (2013). Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments. Cancer chemotherapy and pharmacology, 72(2), 369-78. https://doi.org/10.1007/s00280-013-2206-x
Pauley, Jennifer L, et al. "Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments." Cancer chemotherapy and pharmacology vol. 72,2 (2013): 369-78. doi: https://doi.org/10.1007/s00280-013-2206-x
Pauley JL, Panetta JC, Crews KR, Pei D, Cheng C, McCormick J, Howard SC, Sandlund JT, Jeha S, Ribeiro R, Rubnitz J, Pui CH, Evans WE, Relling MV. Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments. Cancer Chemother Pharmacol. 2013 Aug;72(2):369-78. doi: 10.1007/s00280-013-2206-x. Epub 2013 Jun 13. PMID: 23760811; PMCID: PMC3719000.
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Cancer Chemother Pharmacol. 2013 Aug;72(2):369-78. doi: 10.1007/s00280-013-2206-x. Epub 2013 Jun 13.

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

Cancer chemotherapy and pharmacology

Jennifer L Pauley, John C Panetta, Kristine R Crews, Deqing Pei, Cheng Cheng, John McCormick, Scott C Howard, John T Sandlund, Sima Jeha, Raul Ribeiro, Jeffrey Rubnitz, Ching-Hon Pui, William E Evans, Mary V Relling

Affiliations

  1. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.

PMID: 23760811 PMCID: PMC3719000 DOI: 10.1007/s00280-013-2206-x

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/m(2)/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 < 0.001) and 61 % (p = 0.43) with conventionally dosed therapy. Only 1.3 % of the individualized courses in the standard-/high-risk arm had a Cpss greater than 50 % above the target compared to 7.3 % (p < 0.001) in conventionally dosed therapy. We observed a low rate (8.5 % of courses) of grade 3-4 toxicities. The odds of gastrointestinal toxicity were related to methotrexate plasma concentrations in both the low (p = 0.021)- and standard-/high-risk groups (p = 0.003).

CONCLUSIONS: Individualizing HDMTX based on the clearance from the prior course resulted in fewer extreme Cpss values and less delayed excretion compared to conventional dosing.

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