Page 170 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 5
board (IRB) prior to data sharing. The study protocol of this study is publicly available (as online supplement available with this publication).
Supplementary results
Detailed information of DPYD variant allele carriers not treated according to dosing recommendations
For four patients dosing recommendations were not followed according to protocol. One patient carrying DPYD*2A started with a full dose as genotyping results were not awaited before start of treatment. After one week of treatment the DPYD genotyping result became available and the dose was reduced to 50%. The patient did not experience severe treatment- related toxicity in this course. However, from the third cycle onwards the dose was quickly titrated upwards (75% in the third cycle and 90% in the fourth cycle), hereafter treatment- related toxicity (anorexia grade 2, fatigue grade 3) occurred and the dose was reduced again. A second patient (DPYD*2A carrier) also started with a full dose as genotyping results were not awaited before starting treatment. As results were known the following day, the patient had only taken a full dose for one day, which did not result in severe toxicity. The patient was treated with a 50% dose from the second day onwards. A third patient carrying c.2846A>T, used a full dose for four days, but continued with a 50% dose after an interruption of 5 days. The overall dose intensity of this cycle was approximately 55% and no toxicity occurred. The fourth patient (c.2846A>T carrier) was wrongly treated with a full dose for two cycles due to miscommunication with the patient. The patient experienced severe diarrhea, pancytopenia and sepsis, and passed away.
Pharmacokinetic analyses
A total of 26 DPYD variant allele carriers treated with reduced dose of capecitabine was included in the analysis. Pharmacokinetic results are shown in Supplementary Table 3. In 24 out 26 patients (92%) pharmacokinetic sampling was performed at day 1 of cycle 1. In two patients this was done at day 1 of another cycle, after a resting period of one week without capecitabine intake.
Of five patients who were treated with 5-FU, pharmacokinetic blood samplings was performed as well, but results were considered unreliable, most likely as drawing of blood was not done correctly. Results of the 5-FU treated patients are therefore not included in the analysis.
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