Improved 5-Fluorouracil Chemotherapy in Breast Cancer Patients by Monitoring Dihydropyrimidine Dehydrogenase Activity.

Abstract

Abstract : 5-Fluorouracil (5-FU) is one of the most used chemotherapeutic agents in the treatment of breast cancer. Dihydropyrimidine dehydrogenase (DPD) is the key enzyme in 5-FU catabolism. The major purpose of the project is to characterize the distribution pattern of DPD activity in breast cancer patients, to establish the relationship between DPD activity and 5-FU-associated toxicity, and to improve 5-FU-based chemotherapy in breast cancer patients by monitoring DPD activity. Results from the present study with 336 breast cancer patients demonstrated that DPD activity follows a normal distribution as seen in normal population. However, the mean DPD activity in breast cancer patients was significantly lower than that observed with the general population. Results from the present study with 138 human liver samples demonstrated that liver DPD activity follows a normal distribution, and slight differences among race, gender, and ages were observed. Using a polyclonal antibody against human DPD, we have shown the correlation between DPD activity and the amount of DPD protein, providing the insight of DPD deficiency and the basis for the future clinical use of DPD antibody to quantify DPD activity in cancer patients.