Search

Dihydropyrimidine dehydrogenase DPD is the initial and ratelimiting enzyme in the catabolism of 5fluorouracil 5FU, and it is suggested that patients with a partial deficiency of this enzyme are at risk of developing severe 5FUassociated toxicity. We evaluated the importance of DPD deficiency, gender and the presence of the IVS141G>A mutation in the etiology of 5FU toxicity. In 61 of cases, decreased DPD activity could be detected in peripheral blood mononuclear cells. Furthermore, the number of females 65 in the total group of patients appeared to be higher than the number of males 35 p 0.03. Patients with partial DPD deficiency appeared to have a 3.4fold higher risk of developing grade IV neutropenia than patients with normal DPD activity. Analysis of the DPYDgene of patients suffering from grade IV neutropenia for the presence of the IVS141G>A mutation showed that 50 of the patients investigated were heterozygous or homozygous for the IVS141G>A mutation. Adopting a threshold level for DPD activity of 70 of that observed in the normal population, 14 of the population is prone to the development of severe 5FUassociated toxicity. Below this threshold level, 90 of individuals heterozygous for a mutation in the DPYDgene can be identified. Considering the common use of 5FU in the treatment of cancer, the severe 5FUrelated toxicities in patients with low DPD activity and the apparently high prevalence of the IVS141G>A mutation, screening of patients at risk before administration of 5FU is warranted. © 2002 WileyLiss, Inc.