Page 98 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 4
- Factor 2.6 increase in the percentage of patients with grade III-IV diarrhoea (from 24% to 62%) (S; medium association: false discovery rate 0.3-0.4)
The sensitivity of c.2846A>T for predicting grade III-IV diarrhoea was 4% and the specificity 99%.
- No significant increase in the percentage of patients with grade II-III hand-foot syndrome or with grade III- IV toxicity (NS).
- Decrease in the cumulative dose over the first 6 cycles (S): the average dose decrease increased from 10% to 27% in the lowest-dose cycle and from 10% to 24% in cycle 6.
- No difference in mortality or progression-free survival (NS)
(*1/*6 + *6/*6) versus *1/*1:
- Factor 1.8 increase in the percentage of patients with grade III-IV diarrhoea (from 23% to 41%) (S; medium association: false discovery rate 0.3-0.4)
The sensitivity of *6 (2194G>A) for predicting grade III-IV diarrhoea was 12% and the specificity 95%.
- No significant increase in the percentage of patients with grade II-III hand-foot syndrome or with grade III- IV toxicity (NS).
- No significant increase in dose decreases (NS)
- No difference in mortality or progression-free survival (NS)
(*1/496G + 496G/496G) versus *1/*1:
- Factor 1.4 increase in the percentage of patients with grade III-IV diarrhoea (from 23% to 33%) (S; weak association: false discovery rate < 0.3)
The sensitivity of 496A>G for predicting grade III-IV diarrhoea was 24% and the specificity 84%.
- Factor 1.3 increase in the percentage of patients with grade II-III hand-foot syndrome (from 41% to 53%) (S; weak association: false discovery rate < 0.3) The sensitivity of 496A>G for predicting grade II-III hand-foot syndrome was 22% and the specificity 85%. - No significant increase in the percentage of patients with grade III-IV toxicity (NS).
- No significant increase in dose decreases (NS)
- No difference in mortality or progression-free survival (NS)
*13:
- The percentage *1/*13 was 0% among 43 patients with grade IV-V toxicity or two forms of grade III-V toxicity and 1% in 99 randomly selected patients (NS)
The authors indicated that the lack of association with grade III-IV toxicity for each of the investigated SNPs is likely caused by the high risk in the overall population.
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