Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626417
Title: Efficacy and safety of glucarpidase for routine use after high dose methotrexate in patients with bone sarcoma
Author: Perisoglou, M.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Abstract:
Background: High-dose methotrexate (HD-MTX) is an essential component of osteosarcoma treatment. Despite supportive measures MTX-related toxicity results in delays in subsequent chemotherapy administration and potentially reduced treatment efficacy. Alternative rescue regimens utilising glucarpidase in addition to folinic acid may be of benefit in reducing MTX-induced toxicity. Patients and methods: A double blind randomised crossover clinical trial, GLU 1, was designed and activated to determine the efficacy and safety of routine use of glucarpidase after HD-MTX. To establish the frequency of MTX-induced toxicity so that bespoke study endpoints and sample size could be determined, the medical records of 56 patients with bone sarcoma treated with HD-MTX between 2004 and 2005 at University College Hospital (UCH) were studied. Data were collected on MTX-related toxicity and treatment delays. In a separate review, similar data from 17 patients aged . 40 years, and 25 patients aged < 40 years treated with HD-MTX between 2002 and 2007 at UCH were compared. A high performance liquid chromatography (HPLC) assay was validated for the evaluation of plasma MTX and DAMPA concentrations for trial participants. In GLU 1, patients were randomised to receive two HD-MTX courses with folinic acid rescue (cycle FA) followed by two HD-MTX courses with folinic acid and glucarpidase (cycle glu/FA), or cycle glu/FA first followed by cycle FA. The data of 16 patients enrolled up to the interim analysis of the trial were analysed. Results: MTX-related toxicity resulted in delays in half of subsequent chemotherapy cycles (58% in the ≥ 40 years group and 52% in the < 40 years group). In GLU 1, MTX toxicity resulted in delays in 43% of glu/FA cycles and 77% of FA cycles. The use of glucarpidase was not associated with a reduction in MTX AUC. The incidence and grade of MTX-induced toxicity were similar in glu/FA and FA although more severe grades of mucositis were less frequent in glu/FA cycles. No glucarpidase toxicity was observed. Conclusions: Glucarpidase offers a promising addition for rescue from MTX toxicity and continued clinical evaluation to determine its most effective use is warranted.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.626417  DOI: Not available
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