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A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours

The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (P(k)) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond...

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Detalles Bibliográficos
Autores principales: Rasschaert, M, Schrijvers, D, Van den Brande, J, Dyck, J, Bosmans, J, Merkle, K, Vermorken, J B
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359912/
https://www.ncbi.nlm.nih.gov/pubmed/17486132
http://dx.doi.org/10.1038/sj.bjc.6603776
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author Rasschaert, M
Schrijvers, D
Van den Brande, J
Dyck, J
Bosmans, J
Merkle, K
Vermorken, J B
author_facet Rasschaert, M
Schrijvers, D
Van den Brande, J
Dyck, J
Bosmans, J
Merkle, K
Vermorken, J B
author_sort Rasschaert, M
collection PubMed
description The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (P(k)) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1+d2 q 3 weeks. The starting dose was 120 mg m(−2) per day and dose increments of 20 mg m(−2) were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1–8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m(−2). One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma P(k) values of BM were t(max) 35 min, t(1/2) 49.1 min, V(d) 18.3 l m(−2), and clearance 265 ml min(−1) m(−2). The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7–26%). The MTD of BM in the present dose schedule was 180 mg m(−2) on day 1+2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m(−2) per day.
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spelling pubmed-23599122009-09-10 A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours Rasschaert, M Schrijvers, D Van den Brande, J Dyck, J Bosmans, J Merkle, K Vermorken, J B Br J Cancer Translational Therapeutics The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (P(k)) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1+d2 q 3 weeks. The starting dose was 120 mg m(−2) per day and dose increments of 20 mg m(−2) were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1–8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m(−2). One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma P(k) values of BM were t(max) 35 min, t(1/2) 49.1 min, V(d) 18.3 l m(−2), and clearance 265 ml min(−1) m(−2). The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7–26%). The MTD of BM in the present dose schedule was 180 mg m(−2) on day 1+2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m(−2) per day. Nature Publishing Group 2007-06-04 2007-05-08 /pmc/articles/PMC2359912/ /pubmed/17486132 http://dx.doi.org/10.1038/sj.bjc.6603776 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 Translational Therapeutics
Rasschaert, M
Schrijvers, D
Van den Brande, J
Dyck, J
Bosmans, J
Merkle, K
Vermorken, J B
A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
title A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
title_full A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
title_fullStr A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
title_full_unstemmed A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
title_short A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
title_sort phase i study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359912/
https://www.ncbi.nlm.nih.gov/pubmed/17486132
http://dx.doi.org/10.1038/sj.bjc.6603776
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