DPD-based adaptive dosing of 5-FU in patients with head and neck cancer: impact on treatment efficacy and toxicity

Yang, Chen; Ciccolini, Joseph; Blesius, Aurore; Dahan, Laétitia; Bagarry-Liégey, D.; Brunet, Caroline; Varoquaux, A.; Frances, Nicolas; Marouani, Hafedh; Giovanni, Antoine; Ferri-Dessens, R M; Chefrour, Mohamed; Favre, R.; Duffaud, Florence; Seitz, Jean‐François; Zanaret, M.; Lacarelle, Bruno; Mercier, Cédric

doi:10.1007/s00280-010-1282-4

Cited by 67 publications

(54 citation statements)

References 31 publications

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“…Another method that has shown to potentially increase patient safety of 5-FUbased chemotherapy is the use of the endogenous uracil/ dihydrouracil (U/UH 2 ) plasma ratio as a measure for DPD activity. In patients with head and neck cancer, the initially administered dose of 5-FU was reduced depending on the endogenous U/UH 2 plasma ratio, thereby the rate of severe toxicity was strongly reduced compared with a historical control data set treated with the standard dose of 5-FU (51).…”

Section: Discussionmentioning

confidence: 99%

Relationship between Single Nucleotide Polymorphisms and Haplotypes in DPYD and Toxicity and Efficacy of Capecitabine in Advanced Colorectal Cancer

Deenen

Tol

Burylo

et al. 2011

Clinical Cancer Research

170

153

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Purpose: To explore the effect of dihydropyrimidine dehydrogenase (DPD) single nucleotide polymorphisms (SNP) and haplotypes on outcome of capecitabine.Experimental Design: Germline DNA was available from 568 previously untreated patients with advanced colorectal cancer participating in the CAIRO2 trial, assigned to capecitabine, oxaliplatin, and bevacizumab AE cetuximab. The coding region of dihydropyrimidine dehydrogenase gene (DPYD) was sequenced in 45 cases with grade 3 or more capecitabine-related toxicity and in 100 randomly selected controls (cohort). Most discriminating (P < 0.1) or frequently occurring (>1%) nonsynonymous SNPs were analyzed in all 568 patients. SNPs and haplotypes were associated with toxicity, capecitabine dose modifications, and survival.Results: A total of 29 SNPs were detected in the case-cohort analysis, of which 8 were analyzed in all 568 patients. Of the patients polymorphic for DPYD IVS14þ1G>A, 2846A>T, and 1236G>A, 71% (5 of 7), 63% (5 of 8), and 50% (14 of 28) developed grade 3 to 4 diarrhea, respectively, compared with 24% in the overall population. All patients polymorphic for IVS14þ1G>A developed any grade 3 to 4 toxicity, including one possibly capecitabine-related death. Because of toxicity, a mean capecitabine dose reduction of 50% was applied in IVS14þ1G>A and 25% in 2846A>T variant allele carriers. Patients were categorized into six haplotype groups: one predicted for reduced (10%), and two for increased risks (41% and 33%) for severe diarrhea. Individual SNPs were not associated with overall survival, whereas one haplotype was associated with overall survival [HR (95% CI) ¼ 0.57 (0.35-0.95)].Conclusions: DPYD IVS14þ1G>A and 2846A>T predict for severe toxicity to capecitabine, for which patients require dose reductions. Haplotypes assist in selecting patients at risk for toxicity to capecitabine.

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Section: Discussionmentioning

confidence: 99%

Relationship between Single Nucleotide Polymorphisms and Haplotypes in DPYD and Toxicity and Efficacy of Capecitabine in Advanced Colorectal Cancer

Deenen

Tol

Burylo

et al. 2011

Clinical Cancer Research

170

153

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“…Here, we based our DPD evaluation on a simple and rapid functional testing which clinical relevance had already been demonstrated [5,13]. Several other functional approaches (e.g., uracil breath test, uracil challenge test, to name but a few) to establish the DPD status in patients had been proposed in the literature, with similar benefit compared to genotypic-based techniques [2,14].…”

Section: Discussionmentioning

confidence: 99%

5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases

Cordier

Nau

Ciccolini³

et al. 2011

Cancer Chemother Pharmacol

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“…5-FU concentrations have also been determined by LC-MS/ MS technique for evaluation of DPD enzyme activity [52]. The severe toxicity owing to the 5-FU treatment has been anticipated for the assessment of DPD status in cancer patients [53]. Low plasma levels of 5-FU and relatively higher tegafur (a 5-FU prodrug) levels have been measured in colorectal cancer patients simultaneously.…”

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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DPD-based adaptive dosing of 5-FU in patients with head and neck cancer: impact on treatment efficacy and toxicity

Cited by 67 publications

References 31 publications

Relationship between Single Nucleotide Polymorphisms and Haplotypes in DPYD and Toxicity and Efficacy of Capecitabine in Advanced Colorectal Cancer

Relationship between Single Nucleotide Polymorphisms and Haplotypes in DPYD and Toxicity and Efficacy of Capecitabine in Advanced Colorectal Cancer

5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases

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

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