TY - JOUR
T1 - Decreased dihydropyrimidine dehydrogenase activity in a population of patients with breast cancer
T2 - Implication for 5-fluorouracil-based chemotherapy
AU - Lu, Zhihong
AU - Zhang, Ruiwen
AU - Carpenter, John T.
AU - Diasio, Robert B.
PY - 1998/2
Y1 - 1998/2
N2 - Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU), one of the most widely used chemotherapeutic agents in the treatment of breast cancer. The objective of this study was to determine the population characteristics of DPD activity in patients with breast cancer as well as the frequency of DPD deficiency in this population. DPD activity in peripheral blood mononuclear cells (PBM- DPD) was determined in 360 patients with breast cancer, with the mean PBM- DPD (0.26 ± 0.01 nmol/min/mg protein) being significantly lower than that observed in female controls (0.44 ± 0.02 nmol/min/mg protein; P < 0.01). ANOVA analysis examining the significance of differences in DPD activity among various groups indicated that only disease difference (breast cancer versus normal subjects) was significant after adjustments for race and age. In the present study, 21 (5.8%) patients were considered to he DPD deficient, indicating that this pharmacogenetic syndrome may be more common than anticipated (no DPD-deficient individual was found in the controls). Significantly lower DPD activity in patients with breast cancer may predispose to 5-FU-associated toxicity. These results provide further rationale for individualizing the 5-FU dose, thus reducing the risk of toxicity and/or improving therapeutic efficacy in patients with breast cancer.
AB - Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU), one of the most widely used chemotherapeutic agents in the treatment of breast cancer. The objective of this study was to determine the population characteristics of DPD activity in patients with breast cancer as well as the frequency of DPD deficiency in this population. DPD activity in peripheral blood mononuclear cells (PBM- DPD) was determined in 360 patients with breast cancer, with the mean PBM- DPD (0.26 ± 0.01 nmol/min/mg protein) being significantly lower than that observed in female controls (0.44 ± 0.02 nmol/min/mg protein; P < 0.01). ANOVA analysis examining the significance of differences in DPD activity among various groups indicated that only disease difference (breast cancer versus normal subjects) was significant after adjustments for race and age. In the present study, 21 (5.8%) patients were considered to he DPD deficient, indicating that this pharmacogenetic syndrome may be more common than anticipated (no DPD-deficient individual was found in the controls). Significantly lower DPD activity in patients with breast cancer may predispose to 5-FU-associated toxicity. These results provide further rationale for individualizing the 5-FU dose, thus reducing the risk of toxicity and/or improving therapeutic efficacy in patients with breast cancer.
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M3 - Article
C2 - 9516918
AN - SCOPUS:0031912432
SN - 1078-0432
VL - 4
SP - 325
EP - 329
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -