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

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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Contributeur : LNC - université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mardi 20 mars 2018 - 08:52:06
Dernière modification le : dimanche 26 juin 2022 - 01:54:50

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Katarzyna Morawska, Françoise Goirand, Laurine Marceau, Madeline Devaux, Adèle Cueff, et al.. 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget, Impact journals, 2018, 9 (14), pp.11559-11571. ⟨10.18632/oncotarget.24338⟩. ⟨hal-01737921⟩



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