Page 85 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

The risk of grade ≥ 3 toxicity was higher in combination therapy than in monotherapy and chemo-radiotherapy regimens.
Genotyping:
- 1613x *1/*1 - 18x *1/*2A
Results:
Treatment characteristics of *1/*2A-patients:
- The initial dose varied from 29% to 60% of the full dose (median 46%). The final dose varied from 17% to 91% of the full dose. The median dose per treatment cycle was 48% (range 17% to 91%). All patients were treated with capecitabine.
- 5 patients developed toxicity grade ≥ 3 (first cycle 29% to 60% of the normal dose, final cycle 17% to 60% and maximum 29% to 67%)
- 2 patients developed toxicity grade 0 (first of the two cycles with 29% and second cycle with 59% of the nor-mal dose and all five cycles 48% of the normal dose, respectively)
- 11 patients developed toxicity grade 1 to 2 (first cycle 30% to 50% of the normal dose, final cycle 24% to 91% and maximum 46% to 91%)
- Toxicity was short in duration and well controlled using standard supportive care.
- For 6 patients, the dose was increased during treatment (dose in first cycle 29% to 47% of the normal dose; maxi-mum dose 46% to 91%).
In two of these patients (dose increase from 47% to 53% and from 44% to 67%, respectively), the dose was later reduced to the initial dose again because of toxicity.
- For 3 patients, the initial dose was still too high and had to be reduced further (initial dose 29% to 44% of the normal dose, final dose 17% to 24%).
- Of 4 evaluable patients, 2 achieved a partial response and 2 had stable disease.
In 4 of 5 patients with rectal cancer treated with chemo-radiotherapy, down staging of the tumour from pT3-4 to ypT0-2 was reached.
Percentage of *1/*2A patients with toxicity for reduced dosing compared to full dosing:
4
Supplement
any grade ≥ 3 toxicity
value for
full dosing x 0.38 (S) 73%
In addition, the observed toxicity was short in duration with reduced dosing and usually long- lasting with full dosing.
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