ArticleCancer chemotherapy and pharmacology2013
Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments.
Article in Cancer chemotherapy and pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Treatment of Mature B-ALL and Burkitt Lymphoma (BL) in Adult Patients. BURKIMAB-14.
Who cites it
26 citing papers in PubMed.
- Rituximab administration in pediatric patients with newly diagnosed acute lymphoblastic leukemia.Leukemia · 2023Trial
- Determining success rates of the current pharmacokinetically guided dosing approach of topotecan in pediatric oncology patients.Pediatric blood & cancer · 2019Trial
- Bedside treatment algorithm for safe administration of 24-hour high-dose methotrexate in adult acute lymphoblastic leukemia.Haematologica · 2026Article
- A Model-Informed Early Prediction of Methotrexate-Induced Acute Kidney Injury in Pediatric Patients with Osteosarcoma Using Real-World Data: A Multi-center Pharmacokinetic Study.Clinical pharmacokinetics · 2026Article
- Half-dose glucarpidase: an effective rescue for toxic methotrexate plasma concentrations in a patient with bilateral primary vitreoretinal lymphoma.Annals of hematology · 2026Article
- Neurotoxic effects of the chemotherapeutic drug "methotrexate": a literature review.Annals of medicine and surgery (2012) · 2025Review
- Dose adjustment strategy for high-dose methotrexate-induced toxicities in pediatric acute lymphoblastic leukemia: based on population PK analysis and exposure-toxicity relationship.Cancer chemotherapy and pharmacology · 2025Article
- The Role of Candidate Polymorphisms in Drug Transporter Genes on High-Dose Methotrexate in the Consolidation Phase of the AIEOP-BFM ALL 2009 Protocol.Clinical and translational science · 2025Article
- Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing.Cancer medicine · 2024Article
- Ommaya reservoir use in pediatric ALL and NHL: a review at St. Jude Children's Research Hospital.Cancer chemotherapy and pharmacology · 2024Article
- Integration of genomics, clinical characteristics and baseline biological profiles to predict the risk of liver injury induced by high-dose methotrexate.Frontiers in pharmacology · 2024Article
- Tutorial on model selection and validation of model input into precision dosing software for model-informed precision dosing.CPT: pharmacometrics & systems pharmacology · 2023Article
- Target concentration achievement for efficacy and safety of patients with osteosarcoma treated with high-dose methotrexate based on individual pharmacokinetics: A retrospective study.Oncology letters · 2023Article
- Evaluation of nine formulas for estimating the body surface area of children with hematological malignancies.Frontiers in pediatrics · 2022Article
- MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.Clinical pharmacology and therapeutics · 2020Article
- Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumours.British journal of clinical pharmacology · 2020Article
- Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia.PloS one · 2020Article
- Article
- Emerging roles for clinical pharmacometrics in cancer precision medicine.Current pharmacology reports · 2018Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
purposeIt is advantageous to individualize high-dose methotrexate (HDMTX) to maintain adequate exposure while minimizing toxicities. Previously, we accomplished this through within-course dose adjustments.
methodsIn 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.
resultsIndividualized 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).
conclusionsIndividualizing 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.