Alice Matheux, Laurine Collas, Maelle Grisard, Léa Goulaieff, François Ghiringhelli, Leïla Bengrine-Lefevre, Julie Vincent, Francoise Goirand, Bernard Royer, Antonin Schmitt
{"title":"与尿嘧啶浓度相比,5-氟尿嘧啶的血浆清除率受肾小球滤过率变化的影响更大。","authors":"Alice Matheux, Laurine Collas, Maelle Grisard, Léa Goulaieff, François Ghiringhelli, Leïla Bengrine-Lefevre, Julie Vincent, Francoise Goirand, Bernard Royer, Antonin Schmitt","doi":"10.1007/s00280-024-04732-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration. The aim of our study was therefore to study the influence of renal or hepatic function on 5-FU clearance.</p><p><strong>Patients and methods: </strong>This was a retrospective study, using patients treated with 5-FU between September 1, 2018 to December 1, 2022 in a French Clinical Cancer Center. Patients were included after treatment with 5FU and therapeutic monitoring of 5FU concentrations after each course of chemotherapy. For each patient, DPD phenotyping by uracil concentration measurement was determined before the first course of 5FU. Blood samples were then taken the day after the start of the 5-FU infusion, between 8 and 10 am, for the first three cycles of 5-FU. With the exception of uracil concentration, which was determined only once, the various data were recorded for each course of 5FU chemotherapy performed. Patients with incomplete information (missing one of the above parameters) were excluded from the database.</p><p><strong>Results: </strong>We included 227 patients, corresponding to 227 uracil concentrations and 575 5-FU concentrations. In an original development, our results show for the first time that 5-FU clearance was proportionally correlated with eGFR (calculated according to CKD-EPI formula). Although we failed to demonstrate this hypothesis significantly, we observed that 5-FU clearance may be more dependent on eGFR than on uracil concentration for low uracil concentrations values.</p><p><strong>Conclusion: </strong>Our study reinforces the still poorly accepted idea of the value of focusing on eGFR in 5-FU dose adjustment.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"9"},"PeriodicalIF":2.7000,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.\",\"authors\":\"Alice Matheux, Laurine Collas, Maelle Grisard, Léa Goulaieff, François Ghiringhelli, Leïla Bengrine-Lefevre, Julie Vincent, Francoise Goirand, Bernard Royer, Antonin Schmitt\",\"doi\":\"10.1007/s00280-024-04732-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration. The aim of our study was therefore to study the influence of renal or hepatic function on 5-FU clearance.</p><p><strong>Patients and methods: </strong>This was a retrospective study, using patients treated with 5-FU between September 1, 2018 to December 1, 2022 in a French Clinical Cancer Center. Patients were included after treatment with 5FU and therapeutic monitoring of 5FU concentrations after each course of chemotherapy. For each patient, DPD phenotyping by uracil concentration measurement was determined before the first course of 5FU. Blood samples were then taken the day after the start of the 5-FU infusion, between 8 and 10 am, for the first three cycles of 5-FU. With the exception of uracil concentration, which was determined only once, the various data were recorded for each course of 5FU chemotherapy performed. Patients with incomplete information (missing one of the above parameters) were excluded from the database.</p><p><strong>Results: </strong>We included 227 patients, corresponding to 227 uracil concentrations and 575 5-FU concentrations. In an original development, our results show for the first time that 5-FU clearance was proportionally correlated with eGFR (calculated according to CKD-EPI formula). Although we failed to demonstrate this hypothesis significantly, we observed that 5-FU clearance may be more dependent on eGFR than on uracil concentration for low uracil concentrations values.</p><p><strong>Conclusion: </strong>Our study reinforces the still poorly accepted idea of the value of focusing on eGFR in 5-FU dose adjustment.</p>\",\"PeriodicalId\":9556,\"journal\":{\"name\":\"Cancer Chemotherapy and Pharmacology\",\"volume\":\"95 1\",\"pages\":\"9\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-12-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Chemotherapy and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00280-024-04732-x\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Chemotherapy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00280-024-04732-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.
Objectives: The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration. The aim of our study was therefore to study the influence of renal or hepatic function on 5-FU clearance.
Patients and methods: This was a retrospective study, using patients treated with 5-FU between September 1, 2018 to December 1, 2022 in a French Clinical Cancer Center. Patients were included after treatment with 5FU and therapeutic monitoring of 5FU concentrations after each course of chemotherapy. For each patient, DPD phenotyping by uracil concentration measurement was determined before the first course of 5FU. Blood samples were then taken the day after the start of the 5-FU infusion, between 8 and 10 am, for the first three cycles of 5-FU. With the exception of uracil concentration, which was determined only once, the various data were recorded for each course of 5FU chemotherapy performed. Patients with incomplete information (missing one of the above parameters) were excluded from the database.
Results: We included 227 patients, corresponding to 227 uracil concentrations and 575 5-FU concentrations. In an original development, our results show for the first time that 5-FU clearance was proportionally correlated with eGFR (calculated according to CKD-EPI formula). Although we failed to demonstrate this hypothesis significantly, we observed that 5-FU clearance may be more dependent on eGFR than on uracil concentration for low uracil concentrations values.
Conclusion: Our study reinforces the still poorly accepted idea of the value of focusing on eGFR in 5-FU dose adjustment.
期刊介绍:
Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.