Page 202 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 7
Type of event
Grade 2 Cardio toxicity Grade ≥3 Cardio toxicity
Grade 2 Fatiguee Grade ≥3 Fatiguee
Grouped type of events
Grade 2 GI toxicityf Grade ≥3 GI toxicityf
Grade 2 HEM toxicityh Grade ≥3 HEM toxicityh
Grade 2 Overall toxicityi Grade ≥3 Overall toxicityi
Actions
Chemotherapy changes
Dose reductions Dose increases
Interruptions Prematurely stopped
Treatment-related hospitalization
Days of hospitalization, mean [range]
WT + standarda (N=771) N (%)
21 (2.7) 11 (1.4)
28 (12.6) 2 (0.9)
138 (17.9) 62 (8)
62 (8) 22 (2.9)
252 (32.7) 105 (13.6)
34 (4.4) 4 (0.5) 38 (4.9) 76 (9.9)
60 (7.8) 13 [1─76]
DPYD + standardb (N=34) N (%)
DPYD + reducedc (N=22) N (%)
- -
1 (33.3) 2 (66.7)
5(14.7) 6 (17.6)
7 (20.6) 4 (11.8)
7 (20.6) 8 (23.5)
4 (11.8)j -
-
6 (17.6)
6 (17.6) 23 [6─36]
p=0.045g p=0.015g
- -
4 (28.6) -
6 (27.3) 2 (9.1)
2 (9.1) 2 (9.1)
7 (31.8) 5 (22.7)
2 (9.1)k 2 (9.1)l 1 (4.5) 4 (18.2)
4 (18.2) 4 [2─5]
p=0.904g p=0.083g
a Wild-type patients receiving standard fluoropyrimidine dosages in chemoradiation therapy;
b DPYD variant allele carriers receiving standard fluoropyrimidine dosages in chemoradiation therapy; c DPYD variant allele carriers receiving initially reduced fluoropyrimidine dosages according to current guidelines compared with standard fluoropyrimidine dosages used in chemoradiation therapy;
d Dataof332patientsintotal,dataof5patientsinthegroupofDPYDvariantallelecarrierstreatedwithastand- ard dose and data of 15 patients in the group of DPYD variant allele carriers who received dose reductions; e Dataof239patientsintotal,dataof3patientsinthegroupofDPYDvariantallelecarrierstreatedwithastand- ard dose and data of 14 patients in the group of DPYD variant allele carriers who received dose reductions; f GI toxicity includes diarrhoea, mucositis, nausea, vomiting;
g P-values shown are compared with wild-type patients;
h HEM toxicity includes neutropenia, thrombocytopenia, leukocytopenia;
i Overall toxicity includes diarrhoea, mucositis, nausea, vomiting, neutropenia, thrombocytopenia, leukocytopenia, anaemia, radiation dermatitis, HFS, cardio toxicity, fatigue and other toxicity;
j Dosages were reduced from 100 to 60-77%;
k Dosages were reduced from 70 to 45% and 100 to 50% (applying dosing guidelines 2 days after start of therapy);
l Dosages were increased from 30 to 46% and from 50 to 60%;
m P-values shown are compared with DPYD variant allele carriers who received a standard dose. Abbreviations: DPYD: gene encoding dihydropyrimidine dehydrogenase; GI: gastrointestinal; HFS: hand-foot syndrome; HEM: haematological; WT: wild-type patients.
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p=0.010m