Table 3.
Severe fluoropyrimidine‐related adverse events during total treatment period
| Genotype‐guided cohort | Retrospective sample | |||||||
|---|---|---|---|---|---|---|---|---|
| Noncarrier (N = 1347) | Carrier (N = 47) | P value a | c.1905+1G>A (N = 9) | c.2846A>T (N = 19) | c.1679T>G (N = 1) | c.1236G>A (N = 18) | c.1236 G>A (N = 41) | |
| Initial dose intensity, mean (SD) | 87.4 (15.2) | 52 (18) | NA | 47 (16) | 47 (21) | 43 (NA) | 59 (13) | 85 (17) |
| Dose intensity, mean (SD) | 84.2 (14.7) | 55 (13) | NA | 46 (8) | 55 (15) | 50 (NA) | 59 (12) | 85 (17) |
| Treatment cycles, median (IQR) | 4 (2–6) | 6 (2–7) | 0.201 | 6 (2–8) | 6 (4–8) | 6 (NA) | 4 (2–6) | 2 (2–4) |
| Total severe AEs b (all cycles), N (%) | N (%) | N (%) | N (%) | |||||
| Global c | 418 (31.0) | 11 (23) | 0.265 | 3 (33) | 5 (26) | 0 (0) | 3 (17) | 14 (34) |
| Gastrointestinal | 167 (12.4) | 6 (12) | 0.940 | 2 (22) | 2 (11) | 0 (0) | 2 (11) | 7 (17) |
| Myelosuppression | 157 (11.7) | 6 (12) | 0.816 | 2 (22) | 2 (11) | 0 (0) | 2 (11) | 2 (5) |
| Cardiac | 33 (2.4) | 0 (0) | 0.625 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| HFS | 35 (2.6) | 1 (2) | >0.99 | 0 (0) | 1 (5) | 0 (0) | 0 (0) | 2 (5) |
| Other d | 113 (8.4) | 2 (4) | 0.425 | 1 (11) | 1 (5) | 0 (0) | 0 (0) | 5 (12) |
| AE‐related death e | 10 (0.7) | 0 (0) | >0.99 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Discontinued treatment f | 232 (17.2) | 10 (21) | 0.437 | 2 (22) | 3 (16) | 0 (0) | 5 (28) | 7 (17) |
Abbreviations: AEs, adverse events; HFS, hand‐foot syndrome; IQR, interquartile range; NA, not applicable.
P value for treatment cycles was calculated based on Wilcoxon‐Mann‐Whitney test. P values for fluoropyrimidine‐related AEs calculated using the following tests: Global, Gastrointestinal, Myelosuppression, and Discontinued Treatment utilized χ2 tests; Cardiac, HFS, Other, and AE‐related Death utilized Fisher’s Exact Test.
Grade ≥3 by Common Terminology Criteria for Adverse Events version 5.0.
Global includes all fluoropyrimidine‐related AEs grade ≥3 and fluoropyrimidine‐related deaths. This does not include discontinuation.
Other grade ≥3 AEs included: fatigue, infections, neurotoxicities, and laboratory abnormalities.
At least one fluoropyrimidine‐related AE contributed significantly to death.
Patients discontinuing treatment with fluoropyrimidines due to a fluoropyrimidine‐related AE of any grade.