Oncotarget

Research Papers:

5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer

Katarzyna Morawska, Françoise Goirand, Laurine Marceau, Madeline Devaux, Adèle Cueff, Aurélie Bertaut, Julie Vincent, Leila Bengrine-Lefevre, François Ghiringhelli and Antonin Schmitt _

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Oncotarget. 2018; 9:11559-11571. https://doi.org/10.18632/oncotarget.24338

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Abstract

Katarzyna Morawska1, Françoise Goirand2,3, Laurine Marceau1, Madeline Devaux1, Adèle Cueff1, Aurélie Bertaut1,3, Julie Vincent1, Leila Bengrine-Lefevre1, François Ghiringhelli1,3 and Antonin Schmitt1,3

1Centre Georges-François Leclerc, Dijon, France

2Laboratoire de Pharmacologie/Toxicologie, CHU de Dijon, Dijon, France

3INSERM U1231, University of Burgundy Franche-Comté, Dijon, France

Correspondence to:

Antonin Schmitt, email: antonin.schmitt@u-bourgogne.fr

Keywords: 5-FU; therapeutic drug monitoring; adverse event; GI cancer; pharmacokinetics

Received: September 29, 2017     Accepted: January 23, 2018     Published: January 30, 2018

ABSTRACT

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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