Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity.
OBJECTIVE
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.
Magné
Nicolas
N
Institut Gustave Roussy, Villejuif, France.
Etienne-Grimaldi
Marie-Christine
MC
Cals
Laurent
L
Renée
Nicole
N
Formento
Jean-Louis
JL
Francoual
Mireille
M
Milano
Gérard
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000187:drug effects*; D011110:Polymorphism, Genetic
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil