Page 140 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 4
dose and non-selected patients on the standard dose. In another study, 4 *1/*2A did not develop grade ≥ 3 toxicity at 50% of the standard dose. One of them had previously developed grade ≥ 3 toxicity during the first cycle at the standard dose. One of them tolerated a dose increase to 60%, the other two did not tolerate a dose increase to 80% and 100% respectively. Of the 3 patients with genotype 1236A/1236A, one tolerated a standard dose. A second patient tolerated the treatment after dose reduction to 60% of the standard dose. Another study found a mean tolerated dose of 55% of the standard dose for 2x 1236A/1236A, 1x 1236A/2846T and 1x 2846T/2846T, although in this study a strong variation between patients (and genotypes) was found (17-100% of the standard dose).
Kinetic consequences:
Increase in the AUC of 5-fluorouracil by 103% (16x *1/*2A), 127% (1x 1236A/2846T) or 766% (1x 2846T/2846T).
52-80% decrease in clearance. 69-109% increase in half-life.
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