2551 Background: The UraBT is currently in development as a phenotypic test to screen for DPD deficiency. Following an oral dose of 2-13C-uracil, the UraBT shows a significant relationship between breath 13CO2 metabolite formation and plasma 2-13C-uracil and 2-13C-dihydrouracil pharmacokinetics. We herein describe a novel, potentially more clinically relevant test in which a small oral dose of 2-13C-5-fluorouracil (5-FU) is administered, followed by assessment of breath 13CO2 metabolite formation as previously described for the UraBT. We hypothesize that the FUBT can rapidly assess interindividual variability in 5-FU catabolism and predisposition to 5-FU toxicity. Methods: Over two sessions separated by a seven day washout, a single dose (6mg/kg, p.o.) of 2-13C-uracil or 2-13C-5-FU was administered to patients with stage III-IV colorectal cancer (n = 4). Subsequent to drug administration, in each session, 13CO2 catabolite formation was quantified in the breath over eight hours. In a separate investigation over two sessions separated by a seven day washout, a single dose (3mg/kg, p.o.) of 2-13C-uracil or 213C-5-FU was administered to colorectal cancer patients with previously documented severe (n=2) or moderate (n=2) 5-FU dose-related hematological/gastrointestinal toxicity. Following drug administration 13CO2 catabolite formation was quantified over eight hours. 13CO2 concentration was expressed as Delta Over Baseline (DOB) in all sessions. Results: Compared to the UraBT, the FUBT showed an increased Cmax (50.7 ± 6.6 DOB/mg vs. 36.8 ± 7.8 DOB/mg; mean ± SD) and decreased Tmax (25 ± 4 min vs. 45 ± 6 min) for 13CO2 formation (p<0.05). The FUBT was able to distinguish patients with previously reported severe and moderate 5- FU toxicity, with 13CO2 Cmax values of 35.5 ± 9.5 DOB/mg (mean ± SD) and 59.8 ± 7.3 DOB/mg, respectively. Importantly, FUBT Cmax values positively correlated with DPD activity (rs=1.00, p<0.01). Conclusions: These data lend support to further development of the FUBT as a rapid and informative test to assess DPD activity and to predict susceptibility to severe dose-related 5-FU toxicity. [CA116964] No significant financial relationships to disclose.