Page 90 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 4
outcomes were not. In addition, this indicates that adverse events common to 5-fluorouracil are not the same as 5-FU-induced adverse events.
Genotyping:
- 2532x *1/*1
- 24x *1/*2A
- 26x *1/c.2846A>T
- 1x *2A/c.2846A>T
- 1x *1/274C
- 5x *2A-genotyping failed
- 5x c.2846A>T-genotyping failed
Results:
Risk of grade ≥ 3 toxicity, premature treatment termination and disease free survival for *2A- carriers compared to non-carriers:
any toxicity
any 5-FU toxicity
diarrhoea neutropenia nausea/vomiting fatigue stomatitis/mucosi tis
dehydration leukopenia
febrile neutropenia anorexia
pain thrombocytopeni a
premature treatment termination
dose modification disease free survival
incide nce for non- carrie rs
ORadj = 3.58 (95% 62% CI: 1.01-12.64) (S)
ORadj = 14.91 (95% 33% CI: 4.26-52.18) (S)
NS 12% x 5.7 (S) 11% x 4.2 (S) 4.8% NS 4.8% NS, trend for an 4.2% increase, p=0.09
NS 2.3% NS, trend for an 1.8% increase, p=0.08
NS, trend for an 1.6% increase, p=0.07
NS 1.5% NS 0.8% NS, trend for an 0.3% increase, p=0.08
x 1.7 (S) 26%
NS 74% NS 73%
after 3 year
When restricting the analysis to Caucasians, sex or treatment, the association between *2A and grade ≥ 3 5-FU toxicity remained significant, whereas the association between *2A and grade ≥ 3 overall toxicity did not.
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