Page 201 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Fluoropyrimidine dosages in chemoradiation therapy
guidelines compared with standard fluoropyrimidine dosages used in chemoradiation therapy. One DPYD*2A variant carrier started intravenous 5-FU therapy at a 100% dose before the genotype result became available. When the genotype was known, the administration of 5-FU was prematurely stopped after 2 instead of 4 days. In the second cycle a 50% dose reduction over 4 days was applied. The overall dose intensity of this patient was 49%. In three DPYD*2A carriers initial reduced dosages were increased during treatment. One patient was included in the clinical trial (NCT00838370) before existence of dosing guidelines and started with 30% of the standard total dose, which was increased to 46%. One patient went from 50 to 60% of the standard total dose and for another patient the dose was increased from 50 to 83%. The latter patient was excluded from statistical analyses, due to the substantial dose increase. The c.2846A>T variant carrier who received a dose reduction, was treated with a 60% dose;
d Included are cancers of the colon sigmoidal, rectum, anus, vulva, vagina, cervix, uterus, endometrium, bladder, urethra, prostate and double tumours with one tumour in the pelvic area;
e Included are cancers of the breast, stomach, oesophagus, pancreas, skin and tongue; 7 f Dose intensity was calculated by dividing the received amount of mg of chemotherapy by the initial scheduled amount of mg of chemotherapy.
Abbreviations: BSA: body surface area; DPYD: gene encoding dihydropyrimidine dehydrogenase; 5-FU: 5-fluorouracil; Fr: fractions; GI: gastro-intestinal tract; Gy: gray; WT: wild-type patients.
Table 3. Toxicity of patients per study group
Shown per study group are percentages of several types of (grouped) toxicity after chemoradiation therapy and actions following toxicity. P-values are shown for executed statistical tests.
Type of event
Grade 2 Diarrhoea Grade ≥3 Diarrhoea
Grade 2 Mucositis Grade ≥3 Mucositis
Grade 2 Nausead Grade ≥3 Nausead
Grade 2 Vomitinge Grade ≥3 Vomitinge
Grade 2 Neutropenia Grade ≥3 Neutropenia
Grade 2 Leukocytopenia Grade ≥3 Leukocytopenia
Grade 2 Thrombocytopenia Grade ≥3 Thrombocytopenia
Grade 2 Anaemiad Grade ≥3 Anaemiad
Grade 2 Radiation dermatitisd Grade ≥3 Radiation dermatitisd
Grade 2 HFS Grade 3 HFS
WT + standarda (N=771) N (%)
122 (15.8) 58 (7.5)
51 (6.6) 13 (1.7)
13 (4.2) 2 (0.6)
12 (5.4) 1 (0.5)
8 (1)
12 (1.6)
60 (7.8) 17 (2.2)
6 (0.8) 5 (0.6)
25 (8) 1 (0.3)
77 (24.7) 13 (4.2)
19 (2.5) 5 (0.6)
DPYD + standardb (N=34) N (%)
5 (14.7) 6 (17.6)
2 (5.9) -
2 (40) 1 (20)
2 (66.7) 1 (33.3)
1 (2.9) 2 (5.9)
7 (20.6) 4 (11.8)
- -
1 (20) 1 (20)
1 (20) -
- -
DPYD + reducedc (N=22) N (%)
3 (13.6) 2 (9.1)
2 (9.1) -
1 (6.7) -
1 (7.1) -
1 (4.5) 2 (9.1)
2 (9.1) 2 (9.1)
1 (4.5) -
2 (13.3) -
5 (33.3) -
1 (4.5) -
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