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

Abstract

To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity. One hundred and thirty-one case-reports (81 women, 50 men) with 5FU-related toxicity were analyzed. 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). The IVS14+1G>A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity.