Dihydropyrimidine dehydrogenase activity in cancer patients.
Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of pyrimidines and fluoropyrimidines. The clinical course of 2 patients with suspected DPD deficiency is described. Both patients had significantly delayed clearance of fluorouracil (5-FU), elevated plasma uracil concentrations, and subsequent lethal toxicity. The prevalence of DPD deficiency in the general population is unknown, but given the large number of cancer patients treated with 5-FU, it may be of great clinical significance. Lymphocytes have been previously shown to be a useful marker of systemic DPD activity. Because DPD activity has not been previously reported in a large population of cancer patients using 5-FU as the substrate, we determined DPD activity in lymphocytes from 66 patients with cancer. DPD activity was determined by a sensitive high performance liquid chromatography method. The mean DPD activity (S.D.) in 66 patients with head and neck cancer was 0.189 (0.071) nomol/min/mg protein with wide interpatient variability (range 0.058-0.357). DPD activity was not correlated to age (r = -0.164, P = 0.188). The mean DPD activity in men [0.192 (0.074)] was not significantly different from that in women [0.172 (0.057); t-test P = 0.418]. Likewise, there was no statistical difference in DPD activity in patients who had not received prior chemotherapy [0.195 (0.066)] to patients receiving one or more cycles of chemotherapy [0.186 (0.074); t-test P = 0.638].
Fleming
R A
RA
Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, Nice, France.
Milano
G A
GA
Gaspard
M H
MH
Bargnoux
P J
PJ
Thyss
A
A
Plagne
R
R
Renée
N
N
Schneider
M
M
Demard
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D005472:Fluorouracil / Q000097:blood; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000097:blood / Q000172:deficiency*; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D014498:Uracil / Q000097:blood
D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil