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A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas
In order to achieve higher dosages than previously used in clinical trials, we conducted a phase I trial to determine the maximum tolerated dose (MTD) for the combination of erlotinib and sirolimus for the treatments of recurrent malignant gliomas. Patients with pathologically proven World Health Or...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472078/ https://www.ncbi.nlm.nih.gov/pubmed/22918789 http://dx.doi.org/10.1007/s11060-012-0960-y |
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author | Nghiemphu, Phioanh Leia Lai, Albert Green, Richard M. Reardon, David A. Cloughesy, Timothy |
author_facet | Nghiemphu, Phioanh Leia Lai, Albert Green, Richard M. Reardon, David A. Cloughesy, Timothy |
author_sort | Nghiemphu, Phioanh Leia |
collection | PubMed |
description | In order to achieve higher dosages than previously used in clinical trials, we conducted a phase I trial to determine the maximum tolerated dose (MTD) for the combination of erlotinib and sirolimus for the treatments of recurrent malignant gliomas. Patients with pathologically proven World Health Organization (WHO) grade III glioma and grade IV glioblastoma and radiographically proven tumor recurrence were eligible for this study. Treatments included once daily erlotinib, which was given alone for the first 7 days of treatments, then in combination with once daily sirolimus. Sirolimus was given with a loading dose on day 8 followed by a maintenance dose starting on day 9. Dose-limiting toxicity (DLT) was determined over the first 28 days of treatments, and the MTD was determined in a 3 + 3 classic study design. 19 patients were enrolled, and 13 patients were eligible for MTD determination. The MTD was determined to be 150 mg daily for erlotinib and 5 mg daily (after a 15 mg loading dose) for sirolimus. The DLTs included rash and mucositis (despite maximal medical managements), hypophosphatemia, altered mental status, and neutropenia. The combination of erlotinib and sirolimus is difficult to tolerate at dosages higher than previously reported in phase II trials. |
format | Online Article Text |
id | pubmed-3472078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-34720782012-10-18 A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas Nghiemphu, Phioanh Leia Lai, Albert Green, Richard M. Reardon, David A. Cloughesy, Timothy J Neurooncol Clinical Study In order to achieve higher dosages than previously used in clinical trials, we conducted a phase I trial to determine the maximum tolerated dose (MTD) for the combination of erlotinib and sirolimus for the treatments of recurrent malignant gliomas. Patients with pathologically proven World Health Organization (WHO) grade III glioma and grade IV glioblastoma and radiographically proven tumor recurrence were eligible for this study. Treatments included once daily erlotinib, which was given alone for the first 7 days of treatments, then in combination with once daily sirolimus. Sirolimus was given with a loading dose on day 8 followed by a maintenance dose starting on day 9. Dose-limiting toxicity (DLT) was determined over the first 28 days of treatments, and the MTD was determined in a 3 + 3 classic study design. 19 patients were enrolled, and 13 patients were eligible for MTD determination. The MTD was determined to be 150 mg daily for erlotinib and 5 mg daily (after a 15 mg loading dose) for sirolimus. The DLTs included rash and mucositis (despite maximal medical managements), hypophosphatemia, altered mental status, and neutropenia. The combination of erlotinib and sirolimus is difficult to tolerate at dosages higher than previously reported in phase II trials. Springer US 2012-08-24 2012 /pmc/articles/PMC3472078/ /pubmed/22918789 http://dx.doi.org/10.1007/s11060-012-0960-y Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Clinical Study Nghiemphu, Phioanh Leia Lai, Albert Green, Richard M. Reardon, David A. Cloughesy, Timothy A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
title | A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
title_full | A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
title_fullStr | A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
title_full_unstemmed | A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
title_short | A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
title_sort | dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472078/ https://www.ncbi.nlm.nih.gov/pubmed/22918789 http://dx.doi.org/10.1007/s11060-012-0960-y |
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