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The impact of liver resection on the dihydrouracil: uracil plasma ratio in patients with colorectal liver metastases

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Název: The impact of liver resection on the dihydrouracil: uracil plasma ratio in patients with colorectal liver metastases
Autoři: Jacobs, Bart A W, Snoeren, Nikol, Samim, Morsal, Rosing, Hilde, de Vries, Niels, Deenen, Maarten J, Beijnen, Jos H, Schellens, Jan H M, Koopman, Miriam, van Hillegersberg, Richard
Přispěvatelé: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Rok vydání: 2018
Témata: Aged, 80 and over, Antimetabolites, Antineoplastic/adverse effects, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bevacizumab/adverse effects, Capecitabine/adverse effects, Colorectal Neoplasms/blood, Female, Humans, Liver/surgery, Liver Neoplasms/blood, Male, Middle Aged, Organoplatinum Compounds/adverse effects, Oxaliplatin, Uracil/analogs & derivatives, Taverne
Popis: PURPOSE: The dihydrouracil (DHU):uracil (U) plasma ratio is a promising marker for identification of dihydropyrimidine dehydrogenase (DPD)-deficient patients. The objective of this study was to determine the effect of liver resection on the DHU:U plasma ratio in patients with colorectal liver metastases (CRLM). METHODS: An observational study was performed in which DHU:U plasma ratios in patients with CRLM were analyzed prior to and 1 day after liver resection. In addition, the DHU:U plasma ratio was quantified in six additional patients 4-8 weeks after liver resection to explore long-term effects on the DHU:U plasma ratio. Quantification of U and DHU plasma levels was performed using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. RESULTS: The median (range) DHU:U plasma ratio in 15 patients prior to liver resection was 10.7 (2.6-14.4) and was significantly reduced to 5.5 (< quantification limit (LLOQ-10.5) 1 day after resection (p = 0.0026). This reduction was caused by a decrease in DHU plasma levels from 112.0 (79.8-153) ng/mL to 41.2 (< LLOQ-160) ng/mL 1 day after resection (p = 0.0004). Recovery of the DHU:U plasma ratio occurred 4-8 weeks after liver resection, which was shown by a median (range) DHU:U plasma ratio in six patients of 9.1 (6.9-14.5). CONCLUSION: Liver resection leads to very low DHU:U plasma ratios 1 day after liver resection, which is possibly caused by a reduction in DPD activity. Quantification of the DHU:U plasma ratios directly after liver resection could lead to false-positive identification of DPD deficiency and is therefore not advised.
Druh dokumentu: article in journal/newspaper
Popis souboru: application/pdf
Jazyk: English
ISSN: 0031-6970
Relation: https://dspace.library.uu.nl/handle/1874/376779
Dostupnost: https://dspace.library.uu.nl/handle/1874/376779
Rights: info:eu-repo/semantics/OpenAccess
Přístupové číslo: edsbas.80D5E7F0
Databáze: BASE
Popis
Abstrakt:PURPOSE: The dihydrouracil (DHU):uracil (U) plasma ratio is a promising marker for identification of dihydropyrimidine dehydrogenase (DPD)-deficient patients. The objective of this study was to determine the effect of liver resection on the DHU:U plasma ratio in patients with colorectal liver metastases (CRLM). METHODS: An observational study was performed in which DHU:U plasma ratios in patients with CRLM were analyzed prior to and 1 day after liver resection. In addition, the DHU:U plasma ratio was quantified in six additional patients 4-8 weeks after liver resection to explore long-term effects on the DHU:U plasma ratio. Quantification of U and DHU plasma levels was performed using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. RESULTS: The median (range) DHU:U plasma ratio in 15 patients prior to liver resection was 10.7 (2.6-14.4) and was significantly reduced to 5.5 (< quantification limit (LLOQ-10.5) 1 day after resection (p = 0.0026). This reduction was caused by a decrease in DHU plasma levels from 112.0 (79.8-153) ng/mL to 41.2 (< LLOQ-160) ng/mL 1 day after resection (p = 0.0004). Recovery of the DHU:U plasma ratio occurred 4-8 weeks after liver resection, which was shown by a median (range) DHU:U plasma ratio in six patients of 9.1 (6.9-14.5). CONCLUSION: Liver resection leads to very low DHU:U plasma ratios 1 day after liver resection, which is possibly caused by a reduction in DPD activity. Quantification of the DHU:U plasma ratios directly after liver resection could lead to false-positive identification of DPD deficiency and is therefore not advised.
ISSN:00316970