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A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma
Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360201/ https://www.ncbi.nlm.nih.gov/pubmed/17146474 http://dx.doi.org/10.1038/sj.bjc.6603503 |
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author | Larkin, J M G Hughes, S A Beirne, D A Patel, P M Gibbens, I M Bate, S C Thomas, K Eisen, T G Gore, M E |
author_facet | Larkin, J M G Hughes, S A Beirne, D A Patel, P M Gibbens, I M Bate, S C Thomas, K Eisen, T G Gore, M E |
author_sort | Larkin, J M G |
collection | PubMed |
description | Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(−2) days 1–5 every 28 days and lomustine 60 mg m(–2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. |
format | Text |
id | pubmed-2360201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23602012009-09-10 A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma Larkin, J M G Hughes, S A Beirne, D A Patel, P M Gibbens, I M Bate, S C Thomas, K Eisen, T G Gore, M E Br J Cancer Clinical Study Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(−2) days 1–5 every 28 days and lomustine 60 mg m(–2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. Nature Publishing Group 2007-01-15 2006-12-05 /pmc/articles/PMC2360201/ /pubmed/17146474 http://dx.doi.org/10.1038/sj.bjc.6603503 Text en Copyright © 2007 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Clinical Study Larkin, J M G Hughes, S A Beirne, D A Patel, P M Gibbens, I M Bate, S C Thomas, K Eisen, T G Gore, M E A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
title | A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
title_full | A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
title_fullStr | A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
title_full_unstemmed | A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
title_short | A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
title_sort | phase i/ii study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360201/ https://www.ncbi.nlm.nih.gov/pubmed/17146474 http://dx.doi.org/10.1038/sj.bjc.6603503 |
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