Page 158 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 5
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Table 2. Treatment outcome of patients included in this study
Type of event
DPYD variant allele carriers
Wild-type patients
P-value c.1236G>A c.2846A>T N=51 N=17
DPYD*2A c.1679T>G N=16 N=1
Relative dose intensity whole treatment
[36.7─96.6%] 69.3%
[48.8─127.6%] 96.3%
52..9% 54.2% 51.1% 50.0%
Mean [range]c
Relative dose intensity first cycle
[24.8─96.2%] 33 (39%)
17 (20%)
13 (15%)
[37.2─127.6%] 231 (23%)
86 (8%)
65 (6%)
74.0% 73.4%
NA [50.9─87.5%] [55.3─96.2%] [24.8─81.5%]
Mean [range]c
Overall grade≥3 toxicityd
Grade≥3 gastrointestinal toxicity Grade≥3 hematological toxicity
Grade 3 hand-foot syndromee
Grade≥3 cardiac toxicity
Grade≥3 other treatment-related toxicity Overall grade ≥4 toxicityd
Grade≥4 gastrointestinal toxicity Grade≥4 hematological toxicity
Grade≥4 cardiac toxicity
Grade≥4 other treatment-related toxicity Fluoropyrimidine-related hospitalization Stop of FP due to adverse events Fluoropyrimidine-related death
0.0013a 20 (39%) 8 (47%) 0.00089a 11 (22%) 4 (24%)
5 2 2 0 0 1 0 0 0
(31%) 0 (13%) 0 (13%) 0
N=85 69.1%
N=1,018 94.1%
73.6% 71.6%
NA [50.9─96.6%] [48.8─96.2%] [36.7─74.1%]
1 (1%) 1 (1%) 9 (11%) 4 (5%) 1 (1%) 1 (1%) 0
36 (4%)
9 (1%)
78 (8%) 29 (3%)
8 (1%)
12 (1%)
1 (0%)
9 (1%) 140 (14%) 175 (17%) 3 (0%)
0.0043a 7 0.41b 0 1.0b 1
(14%) 4 (24%) 1 (6%)
0
3 (4%) 16 (19%) 15 (18%) 1 (1%)f
(4%)
1 (6%) 4 (24%) 3 (18%) 1 (6%)f
0 2 4 0
a P-value determined with χ2 test, with Yates’ continuity correction;
b P-value determined with Fisher’s exact test with one-sided probability (with the p-value multiplied by two);
c The relative dose intensity is calculated as the given dose in mg/m2 divided by the standard dose in mg/m2 given for the schedule which was applicable for the patient. The relative dose intensity was calculated for the first cycle alone and duration;
d Overall toxicity includes all toxicities evaluated as possibly, probably or definitely related to fluoropyrimidine-treatment;
0.45a 7 0.49b 3 1.0b 1 1.0b 1
(2%) 0 (14%) 1 (6%) (6%) 1 (6%) (2%) 0 (2%) 0
0 (6%) 0 0 0 0 0 0 (13%) 0 (25%) 0 0
NA 0
0.12b 2
0.26a 10 (20%) 1.0a 8 (16%) 0.55b 0
0 0
indication and treatment for the entire treatment