Page 156 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 5
duration of hospitalization was five days for both DPYD variant allele carriers and wild-type patients (IQR 3─7 days, and 3─10 days, respectively). For 15 out of 85 DPYD variant allele carriers (18%) fluoropyrimidine treatment was stopped due to fluoropyrimidine-related toxicity, compared to 175 out of 1,018 wild-type patients (17%), which was comparable between both groups (p=1.0).
As described above, one c.2846A>T carrier experienced fatal fluoropyrimidine-related toxicity, but the intended dose reductions were not applied for this patient. When disregarding this patient for the critical protocol violation, no treatment-related death occurred in DPYD variant allele carriers. In the wild-type cohort, three patients died due to fluoropyrimidine-related toxicity (0.3%), which is comparable to literature.4,5
Table 1. Demographic and clinical characteristics of patients
Characteristic
Sex
Male
Female
Age
Median [IQR]
Ethnic origin
Caucasian African
Asian
Otherb
Tumor type
Non-metastatic CRC Metastatic CRC BC
GC
Otherc
Type of treatment regimen
CAP mono CAP + RT CAPOX CAP other 5-FU mono 5-FU + RT FOLFOX 5-FU other
BSA
Median [IQR]
DPYD variant allele carriers
N=85
48 (56%) 37 (44%)
63 [54─71] 84 (99%)
0
1 (1%) 0
32 (38%) 24 (28%) 10 (12%) 6 (7%) 13 (15%)
14 (16%) 18 (21%) 31 (36%) 5 (6%)
1 (1%) 6 (7%) 5 (6%) 5 (6%)
1.9 [1.8─2.1]
Wild-type patients
N=1,018
545 (54%) 473 (46%)
64 [56─71] 964 (95%)
19 (2%) 23 (2%) 12 (1%)
440 (43%) 208 (20%) 131 (13%) 57 (6%) 182 (18%)
191 (19%) 246 (24%) 343 (34%) 67 (7%)
1 (0%) 57 (6%) 38 (4%) 75 (7%)
1.9 [1.8─2.1]
Total P-valuea N=1,103
593 (54%) 510 (46%)
0.68
64 [56─71] 0.61 1,048 (95%)
19 (2%) 24 (2%) 12 (1%)
0.61
472 (43%)
232 (21%)
141 (13%) 0.48 63 (6%)
195 (18%)
205 (19%) 264 (24%) 374 (34%) 72 (7%)
2 (0%) 63 (6%) 43 (4%) 80 (7%)
1.9 [1.8─2.1]
table continues
0.40
0.40
0.60
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