Accession Number : ADA319960

Title :   Improving 5-Fluorouracil Chemotherapy in Breast Cancer Patients by Monitoring Dihydropyrimidine Dehydrogenase Activity.

Descriptive Note : Annual rept. 15 Aug 95-14 Aug 96,

Corporate Author : ALABAMA UNIV IN BIRMINGHAM

Personal Author(s) : Lu, Zhihong

PDF Url : ADA319960

Report Date : SEP 1996

Pagination or Media Count : 25

Abstract : The purpose of this project is to improve 5-fluorouracil (5-FU)-based chemotherapy in the treatment of breast cancer by monitoring the key 5-FU metabolic enzyme, dihydropyrimidine dehydrogenase (DPD). In the second year, we continued: 1)to characterize DPD activity in breast cancer patients; 2)to establish the relationship between DPD activity and 5-FU-associated toxicity; and 3)to determine DPD activity in the liver and tumor tissues in cancer patients. DPD activity in peripheral blood mononuclear cells (PBM-DPD) was determined in 360 breast cancer patients, with mean PBM-DPD (0.26 + or - 0.01 nmol/min/mg protein) being significantly lower than that observed in female controls (0.44 + or - 0.02, p<0.005). ANOVA analysis indicates that only disease difference (breast cancer vs. normal subjects) is significant after adjustment for race and age. Nine (3%) patients have DPD % deficiency. Significant lower DPD activity in breast cancer patients may predispose to 5-FU-associated toxicity. DPD activity was also determined in tumor and normal liver specimens from 50 cancer patients. Mean liver DPD activity (0.45 + or - 0.02) was higher than that in normal population (0.37 + or - 0.02) and in tumor tissues (0.34 + or - 0.03, p<0.01). These results should be useful in the future clinical evaluation of 5-FU-based chemotherapy.

Descriptors :   *CLINICAL MEDICINE, *CHEMOTHERAPY, *DEHYDROGENASES, *PYRIMIDINES, *BREAST CANCER, TEST AND EVALUATION, TISSUES(BIOLOGY), DISEASES, NEOPLASMS, POPULATION, MEAN, PATIENTS, LIVER, FEMALES, NUCLEI, BLOOD CELLS.

Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE