Table 2.
Dosage and occurrence of severe toxicity of the four different patient groups.
|
DPYDvariant_no DPDnormal_activity |
DPYDvariant_yes DPDnormal_activity |
DPYDvariant_no DPDlow_activity |
DPYDvariant_yes DPDlow_activity |
DPYD variant_yes total |
DPD low_activity total |
All patients | |
|---|---|---|---|---|---|---|---|
| Number of patients | 182 | 16 | 24 | 6 | 22 | 30 | 228 |
| Mean dose intensity of all treatments | 91% | 78% | 84% | 67% | 75% | 81% | 80% |
| Dose reduction due to adverse effects | 61 (34%) | 3 (19%) | 9 (38%) | 2 (33%) | 5 (23%) | 11(37%) | 75 (33%) |
| Complete stop of fluoropyrimidine treatmenta due to adverse effects | 41 (23%) | 5 (31%) | 6 (25%) | 3 (50%) | 8 (36%) | 9 (30%) | 55 (24%) |
| Dose reduction and/or dose discontinuation due to adverse effects | 76 (42%) | 8 (50%) | 7 (29%) | 1 (17%) | 9 (41%) | 8 (27%) | 92 (40%) |
| Initial dose reduction (first cycle of first treatment) | 34 (19%) | 10 (63%) | 11 (46%) | 5 (83%) | 15 (68%) | 16 (53%) | 60 (26%) |
| Overall grade ≥3 toxicity | 52 (29%) | 4 (25%) | 5 (21%) | 3 (50%) | 7 (32%) | 8 (27%) | 63 (28%) |
| Overall grade ≥3 toxicity for patients with an initial dose reductionb | 7 (21%) | 2 (20%) | 3 (27%) | 2 (40%) | 4 (27%) | 5 (31%) | 14 (23%) |
| Overall grade ≥3 toxicity for patients with a standard initial dosec | 45 (30%) | 2 (33%) | 2 (15%) | 1 (100%) | 3 (43%) | 3 (21%) | 50 (30%) |
DPD: dihydropyrimidine dehydrogenase; DPYD: gene encoding DPD protein.
The dose intensity is defined by the percentage of the standard dose for the specific treatment that was given. The percentages between brackets apply to the total number of patients per group except for a. Groups: DPDnormal_activity = normal DPD enzyme activity, DPDlow_activity = decreased DPD enzyme activity below 8.69 nmol/mg protein/hour, DPYDvariant_no = no variant, DPYDvariant_yes = carrier of one of four variants affecting DPD activity (DPYD*2A (c. 1905+1 G>A; rs3918290), c. 2846A>T p.(Asp949Val); rs67376798), DPYD*13 (c. 1679T>G p.[Ile560Ser]; rs55886062), and c.1129-5923C>G (rs75017182)).
Complete stop of fluoropyrimidines during whole treatment.
The percentages between brackets apply to the group total of “initial dose reduction.”
The percentages between brackets apply to the group total of “standard initial dose.”