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

Yang, Qin; Bi, Yunli; Li, Xiaoqian; Liu, Qian; Ma, Jian; Zhang, Chengliang; Zhang, Jinlin; He, Guangzhao

doi:10.1136/ejhpharm-2019-001862

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…Used in tandem with genotyping, phenotyping and TDM could capture more patients at risk of fluoropyrimidine toxicity. TDM has been shown to be useful in improving the pharmacokinetic interindividual variability and safety of 5-FU (Yang et al, 2020). TDM could also prevent underdosing in dose-reduced DPYD variant carriers and would be a way to escalate doses in those that tolerate reduced doses safely.…”

Section: Discussionmentioning

confidence: 99%

Implementation of pharmacogenetic testing in oncology: DPYD-guided dosing to prevent fluoropyrimidine toxicity in British Columbia

Wu,

Anderson,

Hughesman

et al. 2023

Front. Pharmacol.

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Background: Fluoropyrimidine toxicity is often due to variations in the gene (DPYD) encoding dihydropyrimidine dehydrogenase (DPD). DPYD genotyping can be used to adjust doses to reduce the likelihood of fluoropyrimidine toxicity while maintaining therapeutically effective drug levels.Methods: A multiplex QPCR assay was locally developed to allow genotyping for six DPYD variants. The test was offered prospectively for all patients starting on fluoropyrimidines at the BC Cancer Centre in Vancouver and then across B.C., Canada as well as retrospectively for patients suspected to have had an adverse reaction to therapy. Dose adjustments were made for variant carriers. The incidence of toxicity in the first three cycles was compared between DPYD variant allele carriers and non-variant carriers. Subsequent to an initial implementation phase, this test was made available province-wide.Results: In 9 months, 186 patients were tested and 14 were found to be heterozygous variant carriers. Fluoropyrimidine-related toxicity was higher in DPYD variant carriers. Of 127 non-variant carriers who have completed chemotherapy, 18 (14%) experienced severe (grade ≥3, Common Terminology Criteria for Adverse Events version 5.0). Of note, 22% (3 patients) of the variant carriers experienced severe toxicity even after DPYD-guided dose reductions. For one of these carriers who experienced severe thrombocytopenia within the first week, DPYD testing likely prevented lethal toxicity. In DPYD variant carriers who tolerate reduced doses, a later 25% increase led to chemotherapy discontinuation. As a result, a recommendation was made to clinicians based on available literature and expert opinion specifying that variant carriers who tolerated two cycles without toxicity can have a dose escalation of only 10%.Conclusion:DPYD-guided dose reductions were a feasible and acceptable method of preventing severe toxicity in DPYD variant carriers. Even with dose reductions, there were variant carriers who still experienced severe fluoropyrimidine toxicity, highlighting the importance of adhering to guideline-recommended dose reductions. Following the completion of the pilot phase of this study, DPYD genotyping was made available province-wide in British Columbia.

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Section: Discussionmentioning

confidence: 99%

Implementation of pharmacogenetic testing in oncology: DPYD-guided dosing to prevent fluoropyrimidine toxicity in British Columbia

Wu,

Anderson,

Hughesman

et al. 2023

Front. Pharmacol.

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“…4,5,13 However, pharmacokinetic studies on selected drugs found insignificant impacts on exposure levels, 14,47,48 which are correlated to efficacy and toxicity. 49…”

Section: Discussionmentioning

confidence: 99%

“…4,5,13 However, pharmacokinetic studies on selected drugs found insignificant impacts on exposure levels, 14,47,48 which are correlated to efficacy and toxicity. 49 Although the PBC construct did not significantly predict high acceptance, technological support was discussed greatly in the open-ended comments. It also had the secondhighest agreement among respondents and within the pharmacy profession.…”

Section: Facilitators and Barriersmentioning

confidence: 99%

Determining acceptance and perceptions of chemotherapy dose banding in an ambulatory cancer centre

Ho,

Jo Lene,

Yap

et al. 2023

J Oncol Pharm Pract

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Introduction Despite the advantages of dose banding (DB) and numerous plans to adopt this practice, uptake of DB is still poor. As opinions of healthcare professionals were deemed essential in DB's acceptance, this study surveyed key stakeholders to determine the acceptance, facilitators, and barriers of DB in chemotherapy to improve its implementation. Methods A cross-sectional study at the National Cancer Centre Singapore, involving physicians, nurses, and pharmacy staff, was conducted in February 2022. The Theory of Planned Behaviour was adapted to design a survey questionnaire to obtain the acceptance, facilitators, and barriers of DB. Additional questions on maximum acceptable dose variance and essential criteria for selecting drugs for DB were included. Results A total of 93 participants responded, with a mean 9.75 ± 7.37 years of clinical experience. Less than half have heard of DB while few had prior experience. Drug cost was the top selection criteria for DB, followed by toxicity, therapeutic index, frequency of use and drug wastage. Acceptance rate of DB was 41.9%, with majority agreeing to use DB in various drugs but to determine patient suitability before usage. Being greatly affected by subjective norms, having a positive outlook for DB's impacts, and no effect on toxicity significantly influenced acceptance. Conclusion Prior to implementing DB at the institutional level, educational training addressing concerns over toxicity, and providing technological support can help improve acceptance. Future studies can involve patients’ perspectives and more institutions for greater diversity in opinions.

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“…In an additional set of experiments, we used our ToC system to simulate typical colorectal chemotherapy. We perfused 5-FU for 46 h, the same time that it is administered in human colorectal cancer patients treated with chemotherapy [39][40][41][42][43]. 5-FU is a widely used drug in cancer treatment, especially colorectal cancer.…”

Section: Suitability Of the Tumor-on-chip System For Drug Testingmentioning

confidence: 99%

3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays

et al. 2023

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Tumor-on-chips have become an effective resource in cancer research. However, their widespread use remains limited due to issues related to their practicality in fabrication and use. To address some of these limitations, we introduce a 3D-printed chip, which is large enough to host ~1 cm3 of tissue and fosters well-mixed conditions in the liquid niche, while still enabling the formation of the concentration profiles that occur in real tissues due to diffusive transport. We compared the mass transport performance in its rhomboidal culture chamber when empty, when filled with GelMA/alginate hydrogel microbeads, or when occupied with a monolithic piece of hydrogel with a central channel, allowing communication between the inlet and outlet. We show that our chip filled with hydrogel microspheres in the culture chamber promotes adequate mixing and enhanced distribution of culture media. In proof-of-concept pharmacological assays, we biofabricated hydrogel microspheres containing embedded Caco2 cells, which developed into microtumors. Microtumors cultured in the device developed throughout the 10-day culture showing >75% of viability. Microtumors subjected to 5-fluorouracil treatment displayed <20% cell survival and lower VEGF-A and E-cadherin expression than untreated controls. Overall, our tumor-on-chip device proved suitable for studying cancer biology and performing drug response assays.

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

Cited by 4 publications

References 14 publications

Implementation of pharmacogenetic testing in oncology: DPYD-guided dosing to prevent fluoropyrimidine toxicity in British Columbia

Implementation of pharmacogenetic testing in oncology: DPYD-guided dosing to prevent fluoropyrimidine toxicity in British Columbia

Determining acceptance and perceptions of chemotherapy dose banding in an ambulatory cancer centre

3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays

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