Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice

Wilhelm, Martin; Mueller, Lothar; Miller, Michael Craig; Link, Karin; Holdenrieder, Stefan; Bertsch, Thomas; Kunzmann, Volker; Stoetzer, Oliver J.; Suttmann, Ingo; Braess, Jan; Birkmann, Josef; Roessler, Max; Moritz, B.; Kraff, Stefanie; Salamone, Salvatore J.; Jaehde, Ulrich

doi:10.1016/j.clcc.2016.04.001

Cited by 51 publications

(72 citation statements)

References 38 publications

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“…Furthermore, 5FU has a narrow therapeutic index with severe toxicities tending to occur with AUC values > 25 mg h/L during continuous venous infusion [20]. Therefore, therapeutic drug monitoring is considered valuable to achieve optimal 5FU exposure with minimal serious toxicity [21].…”

Section: Introductionmentioning

confidence: 99%

Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic–pharmacodynamic model in gastrointestinal cancer patients

Arshad

Ploylearmsaeng

Karlsson

et al. 2020

Cancer Chemother Pharmacol

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Purpose To describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach. Methods Thirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m 2 /day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m 2 /day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM. Absolute leukocyte counts were described by a semimechanistic myelosuppression model. Covariate relationships were evaluated to explain the possible sources of variability in 5FU pharmacokinetics and pharmacodynamics. Results Total clearance of 5FU correlated with body surface area (BSA). Population estimate for total clearance was 249 L/h. Clearances of 5FU and 5FUH2 fractionally changed by 77%/m 2 difference from the median BSA. 5FU central and peripheral volumes of distribution were 5.56 L and 28.5 L, respectively. Estimated 5FUH2 clearance and volume of distribution were 121 L/h and 96.7 L, respectively. Baseline leukocyte count of 6.86 × 10 9 /L, as well as mean leukocyte transit time of 281 h accounting for time delay between proliferating and circulating cells, was estimated. The relationship between 5FU plasma concentrations and absolute leukocyte count was found to be linear. A higher degree of myelosuppression was attributed to combination therapy (slope = 2.82 L/mg) with cisplatin as compared to 5FU monotherapy (slope = 1.17 L/mg). Conclusions BSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin.

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Section: Introductionmentioning

confidence: 99%

Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic–pharmacodynamic model in gastrointestinal cancer patients

Arshad

Ploylearmsaeng

Karlsson

et al. 2020

Cancer Chemother Pharmacol

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show abstract

“…AUC>30 mg*h/L indicated an increased risk of severe adverse reaction; thus, reducing the subsequent 5-FU dose may be necessary. 9 Mean AUC represents average AUC obtained per patient per time.…”

Section: -Fu Plasma Concentration Monitoring Resultsmentioning

confidence: 99%

“…However, when 5-FU AUC is lower than the target, subsequent 5-FU dosage should be increased; otherwise, 5-FU dosage should be reduced. [6][7][8][9][10][11] Since March 2015, our hospital has been using 5-FU plasma concentration monitoring with the aim of exploring its reference value and comparing its clinical efficacy and safety for patients with advanced colorectal cancer in China. Herein, we reviewed all patients who underwent 5-FU plasma concentration monitoring from the initiation of this technology to August 2018.…”

Section: Introductionmentioning

confidence: 99%

A retrospective analysis of plasma concentration monitoring of fluorouracil in patients with advanced colorectal cancer

Yang

et al. 2019

Eur J Hosp Pharm

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“…Although the main anticancer mechanism of 5-FU is through irreversible inhibition of thymidylate synthase, oxidative stress has also been proposed to play a key role. Accordingly, several reports have revealed that 5-FU increases intracellular level of ROS [3,9,18,19]. In general, cancer cells are less sensitive to ROS, suggesting that the ability to detoxify ROS could be advantageous for tumor development.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of phosphoserine phosphatase enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer

Xun

Yang

2016

Biochemical and Biophysical Research Communications

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Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice

Cited by 51 publications

References 38 publications

Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic–pharmacodynamic model in gastrointestinal cancer patients

Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic–pharmacodynamic model in gastrointestinal cancer patients

A retrospective analysis of plasma concentration monitoring of fluorouracil in patients with advanced colorectal cancer

Inhibition of phosphoserine phosphatase enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer

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