Journal
CLINICAL CANCER RESEARCH
Volume 10, Issue 8, Pages 2652-2658Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-03-0374
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Funding
- NCI NIH HHS [CA 62164] Funding Source: Medline
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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-C-13-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-C-13-uracil (6 mg/kg). (CO2)-C-13 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) C-max, T-max, delta over baseline values at 50 min (DOB50) and cumulative percentage of C-13 dose recovered (PDR) for normal, partially, and profoundly DPD-deficient individuals were 186.4 +/- 3.9, 117.1 +/- 9.8, and 3.6 DOB; 52 +/- 2, 100 +/- 18.4, and 120 min; 174.1 +/- 4.6, 89.6 +/- 11.6, and 0.9 DOB50; and 53.8 +/- 1.0, 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-C-13-uracil breath test indices (C-max, T-max, 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.
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