Table 2.
Dose advice for compound heterozygous DPYD variant allele carriers. Shown per patient are DPYD variants, phasing of the DPYD variants, GAS, retrospective DPWG dosing advice based on phasing, DPD enzyme activity, and percentage of DPD enzyme activity considered for dose advice. According to the DPWG guidelines [19], a gene activity score can be given to compound heterozygous patients when phasing is known. Fully functional/reduced functionality = gene activity score of 1.5; fully functional/inactive = gene activity score of 1; reduced functionality/reduced functionality = gene activity score of 1; reduced functionality/inactive = gene activity score of 0.5; inactive/inactive = gene activity score of 0. Abbreviations: DPD: dihydropyrimidine dehydrogenase; GAS: gene activity score; DPWG: Dutch Pharmacogenetic Working Group; X: could not be determined.
| Patient # | DPYD Variants | Phasing | GAS [12] | DPWG Dose Advice (% of Regular Dose) | DPD Activity (nmol/(mg×h)) | Percentage of DPD Activity 1 |
|---|---|---|---|---|---|---|
| 1 | DPYD*2A + c.1236G>A | in trans | 0.5 | 25% | 0.9 | 9% |
| 2 | DPYD*2A + c.2846A>T | in trans | 0.5 | 25% | 6.0 | 60% |
| 3 | c.1236G>A + c.2846A>T | in trans | 1 | 50% | 4.5 | 45% |
| 4 | DPYD*2A + c.2846A>T | unknown | X | X | 0.11 | 1% |
| 5 | DPYD*2A + c.2846A>T | in cis | 1 | 50% | 7.2 | 72% |
| 6 | DPYD*2A + c.1236G>A | unknown | X | X | 3.8 | 38% |
| 7 | DPYD*2A + c.1236G>A | unknown | X | X | 1.6 | 16% |
1 The reference DPD activity ranges from 5.9–14 nmol/(mg×h) [28], and therefore the percentage of DPD activity can be calculated using the average of the reference (9.9 nmol/(mg×h). This percentage could be used as a percentage of the regular dose.