A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity

Ciccolini, Joseph; Mercier, Cédric; Blachon, M.F; Favre, R.; Durand, Alain; Lacarelle, Bruno

doi:10.1111/j.1365-2710.2004.00569.x

Cited by 72 publications

(65 citation statements)

References 32 publications

(32 reference statements)

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“…In addition, the ratio of uracil to dihydrouracil in plasma was subsequently measured as a surrogate marker of DPD activity (the higher the ratio, the lower the activity; ref. 25). This uracil/ dihydrouracil ratio was high, with a value of 4.9, strongly suggesting a DPD deficiency (25), when compared with the Gaussian distribution of previously measured ratios in a nonselected cancer population (n = 60, mean = 1.4).…”

Section: Resultsmentioning

confidence: 89%

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Pharmacogenetics of Capecitabine in Advanced Breast Cancer Patients

Largillier

Étienne-Grimaldi

Formento

et al. 2006

Clinical Cancer Research

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Purpose: Germinal gene polymorphisms can explain a part of the interpatient pharmacodynamic variability of anticancer drugs, particularly fluoropyrimidines. Genes for which polymorphisms may potentially influence pharmacodynamics of fluoropyrimidines, including capecitabine, are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD). Experimental design: The aim of this prospective pilot study was to analyze the effect of TS, MTHFR, and DPD gene polymorphisms on toxicity and efficacy in advanced breast cancer patients receiving capecitabine as monotherapy. Germinal polymorphisms of TS (6 bp deletion in the 3 ¶ region and 28 bp repeats, including G>C mutation in the 5 ¶ region), MTHFR (677C>Tand 1298A>C), and DPD (IVS14 + 1G>A) were determined in 105 consecutive patients. Results: A trend toward a higher global toxicity grade 3 and 4 was observed in patients homozygous for the TS 3RG allele compared with patients heterozygous for the 3RG allele or patients not carrying the 3RG allele (50% versus 19% versus 13% respectively, P = 0.064). The sole patient bearing the DPD IVS14 + 1G>A mutation (heterozygous) deceased from hematologic toxicity. The median response duration was 5.8 months (95% confidence interval, 4.3-7.2). Duration of response was significantly shortened in patients homozygous for the 3RG allele compared with others (P = 0.037).Conclusions: The present data suggest that 3RG3RG breast cancer patients are not good candidates for capecitabine therapy. In addition, attention should be paid to DPD deficiency in breast cancer patients receiving capecitabine. These preliminary data require further confirmation on a larger number of patients.

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Section: Resultsmentioning

confidence: 89%

“…25). This uracil/ dihydrouracil ratio was high, with a value of 4.9, strongly suggesting a DPD deficiency (25), when compared with the Gaussian distribution of previously measured ratios in a nonselected cancer population (n = 60, mean = 1.4). The 5 ¶ TS genotype of this patient was 3RC3RG (class 3).…”

Section: Resultsmentioning

confidence: 89%

Pharmacogenetics of Capecitabine in Advanced Breast Cancer Patients

Largillier

Étienne-Grimaldi

Formento

et al. 2006

Clinical Cancer Research

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“…Among combination therapies, 5-FU and doxorubicin (sold under the brand name Adriamycin) is the most prevalent combination (32). 5-FU, a pyrimidine analogue, is a cytotoxic agent which is extensively used in different solid tumors such as breast, lung and gastrointestinal tract cancers (33,34). Doxorubicin, an anthracycline glycoside, is commonly used as chemotherapeutic agent in various malignant disorders; however, the possibility of the adverse effect of irreversible cardiomyopathy limits its use (35).…”

Section: Discussionmentioning

confidence: 99%

Attenuation effect of Abnormal Savda Munziq on liver and heart toxicity caused by chemotherapy in mice

Aikemu

Amat

Yusup

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Abnormal Savda Munziq (ASMq), an Uighur medicine formula commonly used in the treatment of cancer, has been speculated to possess antioxidative and antiproliferative effects, and to regulate immune activity. The present study was designed to systematically elucidate the toxicity-reducing activity of ASMq in mice undergoing combination chemotherapy with doxorubicin and 5-fluorouracil (5-FU). The mice were divided into normal (saline, 10 ml/kg) and doxorubicin + 5-FU groups (doxorubicin, 2.5 mg/kg; 5-FU, 10 mg/kg on alternate days). In addition, three groups received different doses of ASMq (2, 4 and 8 g/kg), in addition to doxorubicin (2.5 mg/kg) and 5-FU (10 mg/kg) treatment on alternate days. The histology of the heart and liver, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA) concentrations in heart homogenate, and various biochemical parameters of the liver were evaluated. Compared with the normal control group, ASMq dose-dependently improved a number of variables, including body weight, liver index, transaminase and total protein, and partially normalized liver and cardiac pathology. ASMq restored activities of defense antioxidant enzymes SOD and GSH-Px towards normal levels, and decreased MDA concentration in dose-dependent manner. These results demonstrated that ASMq provides significant protection against doxorubicin + 5-FU combination induced hepatotoxicity and cardiotoxicity. Further studies are required to determine the effects of ASMq against doxorubicin + 5-FU-induced toxicity during chemotherapy in vivo.

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“…This concentration range covers the exposure levels presently found in clinical practice. The method was found to be sensitive, simple, cost effective and capable of identifying DPD metabolic phenotype in cancer patient [40]. 5-FU and 5-FUH2 have been measured by LC/MS-MS method, for pharmacokinetics studies in patients treated with Ftorafur (FT).…”

Section: Hybrid Instrumental Techniques For 5-fu Analysis In Biologicmentioning

confidence: 99%

A Critical Review on Clinical Application of Separation Techniques for Selective Recognition of Uracil and 5-Fluorouracil

2015

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The most important objectives that are frequently found in bio-analytical chemistry involve applying tools to relevant medical/biological problems and refining these applications. Developing a reliable sample preparation step, for the medical and biological fields is another primary objective in analytical chemistry, in order to extract and isolate the analytes of interest from complex biological matrices. Since, main inborn errors of metabolism (IEM) diagnosable through uracil analysis and the therapeutic monitoring of toxic 5-fluoruracil (an important anticancerous drug) in dihydropyrimidine dehydrogenase deficient patients, require an ultra-sensitive, reproducible, selective, and accurate analytical techniques for their measurements. Therefore, keeping in view, the diagnostic value of uracil and 5-fluoruracil measurements, this article refines several analytical techniques involved in selective recognition and quantification of uracil and 5-fluoruracil from biological and pharmaceutical samples. The prospective study revealed that implementation of molecularly imprinted polymer as a solid-phase material for sample preparation and preconcentration of uracil and 5-fluoruracil had proven to be effective as it could obviates problems related to tedious separation techniques, owing to protein binding and drastic interferences, from the complex matrices in real samples such as blood plasma, serum samples.

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A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity

Abstract: The method described should be suitable both for detecting patients at high risk of 5-FU toxicity, and for drug level monitoring during chemotherapy.

Cited by 72 publications

References 32 publications

Pharmacogenetics of Capecitabine in Advanced Breast Cancer Patients

Pharmacogenetics of Capecitabine in Advanced Breast Cancer Patients

Attenuation effect of Abnormal Savda Munziq on liver and heart toxicity caused by chemotherapy in mice

A Critical Review on Clinical Application of Separation Techniques for Selective Recognition of Uracil and 5-Fluorouracil

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