European journal of cancer (Oxford, England : 1990) · 2019
Therapeutic drug monitoring as a tool to optimize 5-FU-based chemotherapy in gastrointestinal cancer patients older than 75 years.
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Macaire Pauline, Morawska Katarzyna, Vincent Julie, Quipourt Valérie, Marilier Sophie, Ghiringhelli François, Bengrine-Lefevre Leila, Schmitt Antonin
Аннотация
AIMS: Most clinical trials exclude elderly people, leading to a limited understanding of the benefit-to-risk ratio in this population. Despite existing data regarding the oncological management of elderly receiving fluorouracil (5-FU)-based regimen, our objective was to investigate 5-FU exposure/toxicity relationship in patients ≥75 years and compare the effectiveness of 5-FU therapeutic drug monitoring between elderly and younger patients.
METHODS: Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU-based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surface area, then a blood sample was drawn to measure 5-FU concentration and 5-FU dose was adjusted at the subsequent cycles based on C1 concentration. Assessments of toxicity were performed at the beginning of every cycle.
RESULTS: Seventy-one percent of elderly patients required dose adjustments after C1, compared with 50% for younger patients. Percentages of patients within 5-FU area under the curve range at cycle 2 were 64% and 68%, respectively, for elderly and younger patients. The proportion of elderly patients experiencing severe toxicities fell from 15% at C1 to only 5% at cycle 3.
CONCLUSION: Pharmacokinetic-guided 5-FU-dosing algorithm, leading to an improved tolerability while remaining within therapeutic concentration range, is even more valuable for patients older than 75 years than in younger patients.
METHODS: Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU-based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surface area, then a blood sample was drawn to measure 5-FU concentration and 5-FU dose was adjusted at the subsequent cycles based on C1 concentration. Assessments of toxicity were performed at the beginning of every cycle.
RESULTS: Seventy-one percent of elderly patients required dose adjustments after C1, compared with 50% for younger patients. Percentages of patients within 5-FU area under the curve range at cycle 2 were 64% and 68%, respectively, for elderly and younger patients. The proportion of elderly patients experiencing severe toxicities fell from 15% at C1 to only 5% at cycle 3.
CONCLUSION: Pharmacokinetic-guided 5-FU-dosing algorithm, leading to an improved tolerability while remaining within therapeutic concentration range, is even more valuable for patients older than 75 years than in younger patients.