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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...

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Autores principales: Morawska, Katarzyna, Goirand, Françoise, Marceau, Laurine, Devaux, Madeline, Cueff, Adèle, Bertaut, Aurélie, Vincent, Julie, Bengrine-Lefevre, Leila, Ghiringhelli, François, Schmitt, Antonin
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
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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.
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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
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