Purpose: Dihydropyrimidine dehydrogenase (DPD)-deficient cancer patients have been shown to develop severe toxicity after administration of 5-fluorouracil. Routine determination of DPD activity is limited by time-consuming and labor-intensive methods. The purpose of this study was to develop a simple and rapid 2-13C-uracil breath test, which could be applied in most clinical settings to detect DPD-deficient cancer patients. Experimental Design: Fifty-eight individuals (50 "normal," 7 partially, and 1 profoundly DPD-deficient) ingested an aqueous solution of 2-13C-uracil (6 mg/kg). 13CO2 levels were determined in exhaled breath at various time intervals up to 180 min using IR spectroscopy (UBiT-IR300). DPD enzyme activity and DPYD genotype were determined by radioassay and denaturing high-performance liquid chromatography, respectively. Results: The mean (±SE) Cmax, Tmax, δ over baseline values at 50 min (DOB50) and cumulative percentage of 13C dose recovered (PDR) for normal, partially, and profoundly DPD-deficient individuals were 186.4 ± 3.99 117.1 ± 9.8, and 3.6 DOB; 52 ± 29 100 ± 18.4, and 120 min; 174.1 ± 4.69 89.6 ± 11.6, and 0.9 DOB50; and 53.8 ± 1.09 36.9 ± 2.4, and <1 PDR, respectively. The differences between the normal and DPD-deficient individuals were highly significant (all Ps <0.001). Conclusions: We demonstrated statistically significant differences in the 2-13C-uracil breath test indices (C max, Tmax, DOB50 and PDR) among healthy and DPD-deficient individuals. These data suggest that a single time-point determination (50 min) could rapidly identify DPD-deficient individuals with a less costly and time-consuming method that is applicable for most hospitals or physicians' offices.
ASJC Scopus subject areas
- Cancer Research