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Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer
Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the gastrointestinal tract causing low and variable oral bioavailability. Previously, we demonstrated that oral paclitaxel plus the P-gp inhibitor cic...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360545/ https://www.ncbi.nlm.nih.gov/pubmed/16969354 http://dx.doi.org/10.1038/sj.bjc.6603332 |
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author | Helgason, H H Kruijtzer, C M F Huitema, A D R Marcus, S G ten Bokkel Huinink, W W Schot, M E Schornagel, J H Beijnen, J H Schellens, J H M |
author_facet | Helgason, H H Kruijtzer, C M F Huitema, A D R Marcus, S G ten Bokkel Huinink, W W Schot, M E Schornagel, J H Beijnen, J H Schellens, J H M |
author_sort | Helgason, H H |
collection | PubMed |
description | Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the gastrointestinal tract causing low and variable oral bioavailability. Previously, we demonstrated that oral paclitaxel plus the P-gp inhibitor ciclosporin (CsA) is safe and results in adequate exposure to paclitaxel. This study evaluates the activity, toxicity and pharmacokinetics of paclitaxel combined with CsA in breast cancer patients. Patients with measurable metastatic breast cancer were given oral paclitaxel 90 mg m(−2) combined with CsA 10 mg kg(−1) (30 min prior to each paclitaxel administration) twice on one day, each week. Twenty-nine patients with a median age of 50 years were entered. All patients had received prior treatments, 25 had received prior anthracycline-containing chemotherapy and 19 had three or more metastatic sites. Total number of weekly administrations was 442 (median: 15/patient) and dose intensity of 97 mg m(−2) week(−1). Most patients needed treatment delay and 17 patients needed dose reductions. In intention to treat analysis, the overall response rate was 52%, the median time to progression was 6.5 months and overall survival was 16 months. The pharmacokinetics revealed moderate inter- and low intrapatient variability. Weekly oral paclitaxel, combined with CsA, is active in patients with advanced breast cancer. |
format | Text |
id | pubmed-2360545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23605452009-09-10 Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer Helgason, H H Kruijtzer, C M F Huitema, A D R Marcus, S G ten Bokkel Huinink, W W Schot, M E Schornagel, J H Beijnen, J H Schellens, J H M Br J Cancer Clinical Study Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the gastrointestinal tract causing low and variable oral bioavailability. Previously, we demonstrated that oral paclitaxel plus the P-gp inhibitor ciclosporin (CsA) is safe and results in adequate exposure to paclitaxel. This study evaluates the activity, toxicity and pharmacokinetics of paclitaxel combined with CsA in breast cancer patients. Patients with measurable metastatic breast cancer were given oral paclitaxel 90 mg m(−2) combined with CsA 10 mg kg(−1) (30 min prior to each paclitaxel administration) twice on one day, each week. Twenty-nine patients with a median age of 50 years were entered. All patients had received prior treatments, 25 had received prior anthracycline-containing chemotherapy and 19 had three or more metastatic sites. Total number of weekly administrations was 442 (median: 15/patient) and dose intensity of 97 mg m(−2) week(−1). Most patients needed treatment delay and 17 patients needed dose reductions. In intention to treat analysis, the overall response rate was 52%, the median time to progression was 6.5 months and overall survival was 16 months. The pharmacokinetics revealed moderate inter- and low intrapatient variability. Weekly oral paclitaxel, combined with CsA, is active in patients with advanced breast cancer. Nature Publishing Group 2006-10-09 2006-09-12 /pmc/articles/PMC2360545/ /pubmed/16969354 http://dx.doi.org/10.1038/sj.bjc.6603332 Text en Copyright © 2006 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 Helgason, H H Kruijtzer, C M F Huitema, A D R Marcus, S G ten Bokkel Huinink, W W Schot, M E Schornagel, J H Beijnen, J H Schellens, J H M Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
title | Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
title_full | Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
title_fullStr | Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
title_full_unstemmed | Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
title_short | Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
title_sort | phase ii and pharmacological study of oral paclitaxel (paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360545/ https://www.ncbi.nlm.nih.gov/pubmed/16969354 http://dx.doi.org/10.1038/sj.bjc.6603332 |
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