Cargando…
A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours
The aim of this study is to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PKs) and efficacy of ispinesib (SB-715992) in combination with docetaxel. Patients with advanced solid tumours were treated with ispinesib (6–12 mg m(−2)) and docetaxel (50–75 mg m(−2)). Docetaxel was admi...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2008
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266864/ https://www.ncbi.nlm.nih.gov/pubmed/18319713 http://dx.doi.org/10.1038/sj.bjc.6604264 |
_version_ | 1782151574937665536 |
---|---|
author | Blagden, S P Molife, L R Seebaran, A Payne, M Reid, A H M Protheroe, A S Vasist, L S Williams, D D Bowen, C Kathman, S J Hodge, J P Dar, M M de Bono, J S Middleton, M R |
author_facet | Blagden, S P Molife, L R Seebaran, A Payne, M Reid, A H M Protheroe, A S Vasist, L S Williams, D D Bowen, C Kathman, S J Hodge, J P Dar, M M de Bono, J S Middleton, M R |
author_sort | Blagden, S P |
collection | PubMed |
description | The aim of this study is to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PKs) and efficacy of ispinesib (SB-715992) in combination with docetaxel. Patients with advanced solid tumours were treated with ispinesib (6–12 mg m(−2)) and docetaxel (50–75 mg m(−2)). Docetaxel was administered over 1 h followed by a 1-h infusion of ispinesib on day 1 of a 21-day schedule. At least three patients were treated at each dose level. Blood samples were collected during cycle 1 for PK analysis. Clinical response assessments were performed every two cycles using RECIST guidelines. Twenty-four patients were treated at four dose levels. Prolonged neutropaenia and febrile neutropaenia were dose limiting in six and two patients, respectively. The MTD was ispinesib 10 mg m(−2) with docetaxel 60 mg m(−2). Pharmacokinetic assessment demonstrated concentrations of ispinesib and docetaxel, consistent with published data from single agent studies of the drugs. Seven patients (six hormone refractory prostate cancer (HRPC), one renal cancer) had a best response of stable disease (⩾18 weeks). One patient with HRPC had a confirmed >50% prostatic-specific antigen decrease. The MTD for ispinesib and docetaxel was defined and the combination demonstrated an acceptable toxicity profile. Preliminary PK data suggest no interaction between ispinesib and docetaxel. |
format | Text |
id | pubmed-2266864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-22668642009-09-10 A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours Blagden, S P Molife, L R Seebaran, A Payne, M Reid, A H M Protheroe, A S Vasist, L S Williams, D D Bowen, C Kathman, S J Hodge, J P Dar, M M de Bono, J S Middleton, M R Br J Cancer Clinical Study The aim of this study is to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PKs) and efficacy of ispinesib (SB-715992) in combination with docetaxel. Patients with advanced solid tumours were treated with ispinesib (6–12 mg m(−2)) and docetaxel (50–75 mg m(−2)). Docetaxel was administered over 1 h followed by a 1-h infusion of ispinesib on day 1 of a 21-day schedule. At least three patients were treated at each dose level. Blood samples were collected during cycle 1 for PK analysis. Clinical response assessments were performed every two cycles using RECIST guidelines. Twenty-four patients were treated at four dose levels. Prolonged neutropaenia and febrile neutropaenia were dose limiting in six and two patients, respectively. The MTD was ispinesib 10 mg m(−2) with docetaxel 60 mg m(−2). Pharmacokinetic assessment demonstrated concentrations of ispinesib and docetaxel, consistent with published data from single agent studies of the drugs. Seven patients (six hormone refractory prostate cancer (HRPC), one renal cancer) had a best response of stable disease (⩾18 weeks). One patient with HRPC had a confirmed >50% prostatic-specific antigen decrease. The MTD for ispinesib and docetaxel was defined and the combination demonstrated an acceptable toxicity profile. Preliminary PK data suggest no interaction between ispinesib and docetaxel. Nature Publishing Group 2008-03-11 2008-03-04 /pmc/articles/PMC2266864/ /pubmed/18319713 http://dx.doi.org/10.1038/sj.bjc.6604264 Text en Copyright © 2008 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 Blagden, S P Molife, L R Seebaran, A Payne, M Reid, A H M Protheroe, A S Vasist, L S Williams, D D Bowen, C Kathman, S J Hodge, J P Dar, M M de Bono, J S Middleton, M R A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
title | A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
title_full | A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
title_fullStr | A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
title_full_unstemmed | A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
title_short | A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
title_sort | phase i trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266864/ https://www.ncbi.nlm.nih.gov/pubmed/18319713 http://dx.doi.org/10.1038/sj.bjc.6604264 |
work_keys_str_mv | AT blagdensp aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT molifelr aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT seebarana aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT paynem aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT reidahm aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT protheroeas aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT vasistls aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT williamsdd aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT bowenc aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT kathmansj aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT hodgejp aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT darmm aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT debonojs aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT middletonmr aphaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT blagdensp phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT molifelr phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT seebarana phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT paynem phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT reidahm phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT protheroeas phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT vasistls phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT williamsdd phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT bowenc phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT kathmansj phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT hodgejp phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT darmm phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT debonojs phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours AT middletonmr phaseitrialofispinesibakinesinspindleproteininhibitorwithdocetaxelinpatientswithadvancedsolidtumours |