P-216Primum non nocere: Screening patients for fluoropyrimidine-related toxicity risk: The most effective method

3529 Background: Severe, sometimes fatal, toxicity can occur during the 1 st or 2 nd course of chemotherapy using fluoropyrimidines (FPs), and poses a serious public health problem. FPs carry a 3-5% risk of grade ≥ 3 early toxicities and 0.2% risk of death linked to Dihydropyrimidine Dehydrogenase (DPD) deficiency. Methods: Of 29,000 patients screened since July 2000, 472 were referred to us due to severe toxicity during 1 st round 5-FU, or because pre-screening was done too late. Toxicity evaluation was performed according to the NCI scale of adverse reactions to cancer drugs (0=none, 5=death). Patients were previously 5-FU naïve, had different cancers, and received various protocols, eg. 5FU or Capecitabine; bolus±continuous or per os. The reliability of the following 4 pre-treatment screening tests to predict grade≥ 4 toxicity was assessed: 1) DPYD genotype mutation (*2A,*2B,*7, 13, HapB3) 2) Plasma uracil (U) level, 3) Plasma dihydrouracil/uracil ratio (UH 2 /U) 4) a multiparametric approach with genotyping, UH 2 /U ratio and key patient factors (age, sex, etc.). McNemar’s test with Bonferroni correction was used for statistical analysis. Results: Of the 472 referred patients, 169 had grade 4 or 5 toxicity, of which 41 died from toxicity. 98 had one or plus DPYD mutation: 42(42.9%)*2A; 43(43.9%)*2B; 3(3%)*7; 4(4%)*13; 8(8.16%) HapB3; 1 was homozygous *2A. Data below compare the 4 screening methods for predicting grade 4-5 toxicity. Conclusions: The multiparametric approach is statistically (p<0.0001) the most efficient in terms of preventing grade 4 and 5 toxicity (death) due to 5-FU treatment. Around 290,000 patients are treated with 5-FU per year in the USA. Assuming a 0.2% mortality rate due to toxicity, around 580 lives could be saved per year using the multiparametric pre-treatment test. [Table: see text]