Table 4.
Relative risk of grade ≥3 FP-related toxicity in DPYD variant carriers compared with wild type and in patients with elevated uracil concentrations (≥16 ng/ml) compared with normal values
|
DPYD genotype | ||
|---|---|---|
| Relative risk versus wild type in each group | Intervention (DPYD-guided doses) | Control group (normal dose) |
| DPYD∗2Aa | 1 patient (grade 3 tox) | 3.42 (2.2-5.29) (n = 8) |
| DPYD∗13 | 0.55 (0.15-2.00) (n = 3) | 1 patient (no tox) |
| D949V | 0.60 (0.10-3.65) (n = 6) | 0.44 (0.03-6.11) (n = 3) |
| HapB3b | 0.55 (0.15-1.99) (n = 13) | 1.02 (0.53-2.01) (n = 30) |
| All DPYD variants | 0.82 (0.37-1.82) (n = 22) | 1.29 (0.77-2.18) (n = 42) |
| Uracil intervention group | |||
|---|---|---|---|
| Patients with ≥16 ng/ml versus normal uracil | All patients, n = 200 | Wild-type patients (normal dose), n = 180 | DPYD variants (reduced doses) FP, n = 20 |
| ≥16 ng/ml | 1.97 (1.13-3.44) (n = 13) | 1.96 (1.09-3.54) (n = 11) | 2.25 (0.44-11.52) (n = 2) |
| >150 ng/ml | No patients found | ||
All data reported with 95% confidence intervals.
FP, (5-fluorouracil, capecitabine, tegafur(S-1)); Tox, toxicity.
a
Includes one patient compound heterozygous for DPYD∗2A and HapB3.
b
Includes two patients homozygous for HapB3 and one patient compound heterozygous for DPYD∗2A and HapB3.