Page 88 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 4
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except for Loganayagam 2013. After exclusion of Loganayagam 2013, the p-value was 0.0433.
The effect of *13 on risk of severe toxicity seemed similar in studies with long and short timeframes. The sensitivity of *13 in prediction of grade ≥ 3 toxicity was 0.3% and the positive predictive value 46%.
Risk of grade ≥ 3 toxicity for (*1/c.1236A>G +
c.1236A>G/c.1236A>G) compared to *1/*1:
incidenc
any toxicity haematological
toxicity gastrointestinal toxicity hand-foot syndrome
RRadj (95% CI)
1.59 (1.29-1.97) (S) 2.07 (1.17-3.68) (S)
2.04 (1.49-2.78) (S)
NS (also for the sub- group treated with capecitabine)
e for *1/*1 (% of patients) 22%
There was no significant heterogeneity between the studies.
There was no indication of publication bias.
The results for any toxicity were similar when patients carrying *2A and/or c.2846A>T were excluded from the meta-analysis. The association remained significant after exclusion of any study from the meta-analysis.
The effect of c.1236A>G on risk of severe toxicity seemed similar in studies with long and short timeframes.
The sensitivity of c.1236A>G in prediction of grade ≥ 3 toxicity was 6.4% and the positive predictive value 41%.
The meta-analysis of the case-control studies did not show a significant result, probably due to the smaller number of patients.
The authors reported to have treated 3 patients with genotype c.1236A>G/c.1236A>G safely with low dose capecitabine (825 mg/m2 twice a day).
Risk of grade ≥ 3 toxicity for *2A-carriers compared
to *1/*1:
any toxicity
The heterogeneity between the studies was significant and strong.
RRadj (95% CI) incidenc e for
*1/*1 (% of patients)
2.85 (1.75-4.62) (S) 29%
table continues