Page 157 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Characteristic
WHO performance status
0
1
2 NS d
Number of treatment cycles
Median [IQR]
DPYD status
Wild-type c.1236G>A heterozygous c.2846A>T heterozygous DPYD*2A heterozygous c.1679T>G heterozygous
DPYD variant allele carriers
N=85
39 (46%) 36 (42%) 4 (5%)
6 (7%)
4 [1─8] 0
51 (60%) 17 (20%) 16 (19%) 1 (1%)
Wild-type patients
N=1,018
515 (51%) 412 (40%) 38 (4%) 53 (5%)
3 [1─8] 1,018 (100%)
0 0 0 0
Total N=1,103
554 (50%) 448 (41%) 42 (4%) 59 (5%)
3 [1─8] 1,018 (92%)
51 (5%) 17 (2%) 16 (1%) 1
P-valuea
0.68 0.97
NA
5
Safety analysis on DPYD genotype-guided dosing
a P-value comparing DPYD variant allele carriers to DPYD wild-type patients. A Kruskal-Wallis rank sum test was used for age, BSA, and number of treatment cycles, a Fisher’s exact test was used for ethnic origin and WHO performance status and a χ2 test for sex, tumor type, and treatment regimen;
b Other ethnic origins included Hispanic descent, mixed-racial parentage and unknown ethnic origin;
c Other tumor types included anal cancer, esophageal cancer, head and neck cancer, pancreas cancer, bladder cancer, unknown primary tumor, vulva carcinoma, and several rare tumor types;
d WHO performance status was not specified for these patients, but was either 0, 1, or 2, as this was required by the inclusion criteria of the study.
Abbreviations: 5-FU mono: 5-fluorouracil monotherapy; 5-FU other: 5-fluorouracil combined with other anticancer drugs (excluding the FOLFOX regimen); 5-FU + RT: 5-fluorouracil combined with radiotherapy (with or without mitomycin); BC: breast cancer; BSA: body surface area; CAP mono: capecitabine monotherapy (with or without bevacizumab); CAPOX: capecitabine combined with oxaliplatin (with or without bevacizumab); CAP other: capecitabine combined with other anticancer drugs; CAP + RT: capecitabine combined with radiotherapy (with or without mitomycin); CRC: colorectal cancer; DPYD: gene encoding dihydropyrimidine dehydrogenase; FOLFOX: 5-fluorouracil combined with oxaliplatin and leucovorin (with or without bevacizumab); GC: gastric cancer; IQR: interquartile range; NA: not applicable; NS: not specified.
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