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Case Reports
. 2007 Aug;64(2):237-40.
doi: 10.1111/j.1365-2125.2007.02869.x. Epub 2007 Mar 1.

Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity

Nicolas Magné  1 , Marie-Christine Etienne-Grimaldi, Laurent Cals, Nicole Renée, Jean-Louis Formento, Mireille Francoual, Gérard Milano
Affiliations
Case Reports

Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity

Nicolas Magné et al. Br J Clin Pharmacol. 2007 Aug.

Abstract

Aims: To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity.

Methods: One hundred and thirty-one case-reports (81 women, 50 men) with 5FU-related toxicity were analyzed.

Results: The lower the DPD activity (10-504 pmol min(-1) mg(-1)), the higher the toxicity grade was scored (P < 0.01). Toxicity-related deaths occurred in nine patients (eight women) who significantly expressed lower DPD activity than other patients. Two of the deceased patients had normal DPD activity. The IVS14+1G>A mutation, analyzed in 93 patients, was detected in two patients (nonlethal toxicity).

Conclusions: The IVS14+1G>A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity.

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Figures

Figure 1
Figure 1
Frequency distribution of PBMC-DPD activity in 131 cases of 5FU-related toxicity (1B (▪), mean 200, median 188, range 10–504 pmol min−1 mg−1) and in our previous population study conducted on 185 unselected cancer patients (1A (formula image), mean 222, median 211, range 65–559 pmol min−1 mg−1) [4]
See this image and copyright information in PMC

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