Therapeutic drug monitoring as a tool to optimize 5-FU–based chemotherapy in gastrointestinal cancer patients older than 75 years

Macaire, Pauline; Morawska, Katarzyna; Vincent, Julie; Quipourt, Valérie; Marilier, Sophie; Ghiringhelli, François; Bengrine-Lefèvre, Léïla; Schmitt, Antonin

doi:10.1016/j.ejca.2019.01.102

Cited by 23 publications

(15 citation statements)

References 48 publications

(51 reference statements)

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“…It was concluded that pharmacokinetic‐guided dose adjustment of 5FU was practical and feasible and should become the standard of care 15 . Further studies since this meta‐analysis was performed have also demonstrated the usefulness of TDM and pharmacokinetic‐guided dosing 28–30 . Based on the evaluation of the clinical evidence for 5FU TDM, the IATDMCT now strongly recommends TDM for the management of 5FU therapy in CRC and HNC patients receiving common 5FU regimens 27 …”

Section: Approaches For Precision Dosing Of 5fu and Capecitabinementioning

confidence: 99%

Overcoming barriers to implementing precision dosing with 5‐fluorouracil and capecitabine

Schneider

Galettis

Martin

2021

Brit J Clinical Pharma

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Despite advances in targeted cancer therapy, the fluoropyrimidines 5-fluorouracil (5FU) and capecitabine continue to play an important role in oncology. Historically, dosing of these drugs has been based on body surface area. This approach has been demonstrated to be an imprecise way to determine the optimal dose for a patient. Evidence in the literature has demonstrated that precision dosing approaches, such as DPD enzyme activity testing and, in the case of intravenous 5FU, pharmacokineticguided dosing, can reduce toxicity and yield better patient outcomes. However, despite the evidence, there has not been uniform adoption of these approaches in the clinical setting. When a drug such as 5FU has been used clinically for many decades, it may be difficult to change clinical practice. With the aim of facilitating change of practice, issues and barriers to implementing precision dosing approaches for 5FU and capecitabine are identified and discussed with possible solutions proposed.

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Section: Approaches For Precision Dosing Of 5fu and Capecitabinementioning

confidence: 99%

Overcoming barriers to implementing precision dosing with 5‐fluorouracil and capecitabine

Schneider

Galettis

Martin

2021

Brit J Clinical Pharma

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“…43 It is possible to skip the test-dose step and use the first cycle to adapt dosing on the subsequent courses. 44 PK-guided dosing of 5-FU has proven its clinical relevance, 45 especially in elderly patients, 46 while being cost-effective. 47 With oral targeted therapies, TDM has repeatedly demonstrated how it could help to predict and optimize clinical outcome.…”

Section: Tdmmentioning

confidence: 99%

Towards Rational Cancer Therapeutics: Optimizing Dosing, Delivery, Scheduling, and Combinations

Ferrer

Fanciullino

Milano

et al. 2020

Clin Pharma and Therapeutics

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The current trend to personalize anticancer therapies mostly relies on selecting the best drug or combination of drugs to achieve optimal efficacy in patients. In addition to the comprehensive genetic and molecular knowledge of each tumor before choosing the drugs to be given, there is probably much room left for improvement by further personalizing the very modes by which the drugs are given, once they have been carefully selected. In particular, shifting from standard dosing to tailored dosing should help in maintaining drug exposure levels in the right therapeutic window, thus ensuring that the efficacy/toxicity balance is optimal. This paper covers the current knowledge regarding pharmacokinetic/pharmacodynamic relationships of anticancer agents, from decades‐old cytotoxics to the latest immune checkpoint inhibitors, the most frequent sources for long‐neglected interpatient variability impacting on drug exposure levels, and what could be done to achieve real personalized medicine in oncology such as implementing therapeutic drug monitoring with adaptive dosing strategies or using model‐driven modalities for personalized dosing and scheduling.

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“…Anticancer drugs often fail to treat neuroblastoma due to the respective differences in the phenotypic profiles of tumors (Maeda and Khatami, 2018;Ngan, 2015;Hiyama and Hiyama, 2005). To optimize therapeutic outcomes given the individual differences, drug stability and efficacy tests using human cells in the form of 2-dimensional (2D) cell cultures or xenografts are commonly performed prior to the treatment (Niu and Wang, 2015;Macaire et al, 2019;Zanoni et al, 2016). However, drug responses in patients differ from those observed in cellular model systems.…”

Section: Introductionmentioning

confidence: 99%

DNA repair and cholesterol-mediated drug efflux induce dose-dependent chemoresistance in nutrient-deprived neuroblastoma cells

et al. 2021

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Summary Neuroblastoma is a solid, heterogeneous pediatric tumor. Chemotherapy is widely used to treat neuroblastoma. However, dose-dependent responses and chemoresistance mechanisms of neuroblastoma cells to anticancer drugs remain challenging. Here, we investigated the dose-dependent effects of topotecan on human neuroblastoma cells (SK-N-SH, SH-SY5Y, and SK-N-BE) under various nutrient supply conditions. Serum-starved human neuroblastoma cells showed reduced toxicity. Their survival rate increased upon treatment with a high concentration (1 μM) of topotecan. Quantitative profiling of global and phosphoproteome identified 12,959 proteins and 48,812 phosphosites, respectively, from SK-N-SH cells. Network analysis revealed that topotecan upregulated DNA repair and cholesterol-mediated topotecan efflux, resulting in topotecan resistance. Results of DNA damage assay, cell cycle, and quantitative analyses of membrane cholesterol supported the validity of these resistance factors and their applicability to all neuroblastoma cells. Our results provide a model for high dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.

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Therapeutic drug monitoring as a tool to optimize 5-FU–based chemotherapy in gastrointestinal cancer patients older than 75 years

Cited by 23 publications

References 48 publications

Overcoming barriers to implementing precision dosing with 5‐fluorouracil and capecitabine

Overcoming barriers to implementing precision dosing with 5‐fluorouracil and capecitabine

Towards Rational Cancer Therapeutics: Optimizing Dosing, Delivery, Scheduling, and Combinations

DNA repair and cholesterol-mediated drug efflux induce dose-dependent chemoresistance in nutrient-deprived neuroblastoma cells

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