Cargando…
5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer
AIMS: 5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10–30% of patients treated with 5-FU-based regimens experien...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837758/ https://www.ncbi.nlm.nih.gov/pubmed/29545919 http://dx.doi.org/10.18632/oncotarget.24338 |
_version_ | 1783304143241216000 |
---|---|
author | Morawska, Katarzyna Goirand, Françoise Marceau, Laurine Devaux, Madeline Cueff, Adèle Bertaut, Aurélie Vincent, Julie Bengrine-Lefevre, Leila Ghiringhelli, François Schmitt, Antonin |
author_facet | Morawska, Katarzyna Goirand, Françoise Marceau, Laurine Devaux, Madeline Cueff, Adèle Bertaut, Aurélie Vincent, Julie Bengrine-Lefevre, Leila Ghiringhelli, François Schmitt, Antonin |
author_sort | Morawska, Katarzyna |
collection | PubMed |
description | AIMS: 5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10–30% of patients treated with 5-FU-based regimens experience severe treatment-related toxicity. In our study, we evaluated the 5-FU exposure-toxicity relationship and investigated the efficacy of PK-guided dosing in increasing tolerability of 5-FU-based chemotherapy. RESULTS: 50.7% of patients required dose adjustments after cycle 1. Percentage of patients within 5-FU AUC range was 49.3%, 66.9%, 61.0% at cycle 1, 2 and 3 respectively (p = 0.002 cycle 1 vs cycle 2). At all 3 cycles, lower incidences of grade I/II toxicities were observed for patients below or within range compared with those above range (19.4% vs 41.3%, p < 0.001 respectively). CONCLUSIONS: Our analysis confirms that the use of BSA-guided dosing results in highly variable 5-FU exposure and strongly suggests that PK-guided dosing can improve tolerability of 5-FU based chemotherapy in patients with gastrointestinal cancers, thus supporting 5-FU therapeutic drug monitoring. METHODS: 155 patients with gastrointestinal cancers, who were to receive 5-FU-based regimens were included in our study. At cycle 1, the 5-FU dose was calculated using patient’s Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FU concentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18–28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle. |
format | Online Article Text |
id | pubmed-5837758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-58377582018-03-15 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer Morawska, Katarzyna Goirand, Françoise Marceau, Laurine Devaux, Madeline Cueff, Adèle Bertaut, Aurélie Vincent, Julie Bengrine-Lefevre, Leila Ghiringhelli, François Schmitt, Antonin Oncotarget Research Paper AIMS: 5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10–30% of patients treated with 5-FU-based regimens experience severe treatment-related toxicity. In our study, we evaluated the 5-FU exposure-toxicity relationship and investigated the efficacy of PK-guided dosing in increasing tolerability of 5-FU-based chemotherapy. RESULTS: 50.7% of patients required dose adjustments after cycle 1. Percentage of patients within 5-FU AUC range was 49.3%, 66.9%, 61.0% at cycle 1, 2 and 3 respectively (p = 0.002 cycle 1 vs cycle 2). At all 3 cycles, lower incidences of grade I/II toxicities were observed for patients below or within range compared with those above range (19.4% vs 41.3%, p < 0.001 respectively). CONCLUSIONS: Our analysis confirms that the use of BSA-guided dosing results in highly variable 5-FU exposure and strongly suggests that PK-guided dosing can improve tolerability of 5-FU based chemotherapy in patients with gastrointestinal cancers, thus supporting 5-FU therapeutic drug monitoring. METHODS: 155 patients with gastrointestinal cancers, who were to receive 5-FU-based regimens were included in our study. At cycle 1, the 5-FU dose was calculated using patient’s Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FU concentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18–28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle. Impact Journals LLC 2018-01-30 /pmc/articles/PMC5837758/ /pubmed/29545919 http://dx.doi.org/10.18632/oncotarget.24338 Text en Copyright: © 2018 Morawska et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Morawska, Katarzyna Goirand, Françoise Marceau, Laurine Devaux, Madeline Cueff, Adèle Bertaut, Aurélie Vincent, Julie Bengrine-Lefevre, Leila Ghiringhelli, François Schmitt, Antonin 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
title | 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
title_full | 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
title_fullStr | 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
title_full_unstemmed | 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
title_short | 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
title_sort | 5-fu therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837758/ https://www.ncbi.nlm.nih.gov/pubmed/29545919 http://dx.doi.org/10.18632/oncotarget.24338 |
work_keys_str_mv | AT morawskakatarzyna 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT goirandfrancoise 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT marceaulaurine 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT devauxmadeline 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT cueffadele 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT bertautaurelie 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT vincentjulie 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT bengrinelefevreleila 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT ghiringhellifrancois 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer AT schmittantonin 5futherapeuticdrugmonitoringasavaluableoptiontoreducetoxicityinpatientswithgastrointestinalcancer |