TABLE 3.
Detailed data from included DPYD genotype studies
| First author, year published (PMID) | Study design | Pre‐treatment dose reduction based on DPYD genotype (yes/no) | n with DPYD genotype data | n compound heterzygous or homozygous for DPYD variants | Toxcity (grade ≥ 3) in DPYD wild‐type patients | Toxcity (grade ≥ 3) in DPYD variant carriers (pre‐treatment dose reductions based on DPYD variants) | Toxcity (grade ≥ 3) in DPYD variant carriers without pre‐treatment dose reductions (control group) | Toxicity (grade ≥ 3) in patients homozygous or compound heterozygous for DPYD variants (control group) |
|---|---|---|---|---|---|---|---|---|
| Henricks 2018 (30348537) | Prospective | Yes (DPYD variant carriers received an initial dose reduction of 25% (D949V and HapB3) or 50% (DPYD*2A and DPYD*13)) | 1103 | 4 patients were found. All 4 Excluded before treatment | n = 1018/8% | n = 85/20% | No | 4 patients were found. Excluded. |
| Wigle 2021 (33620159) | Retrospective | Yes. 50% (HapB3 25–50%) | 1435 | No patients were found. | n = 1347/21.1% | n = 47/13% | n = 41/24%. Retrospective samples. Full dose | No patients found |
| Lunenburg 2018 (30361102) | Prospective/Retrospective analysis | Yes/no. 50 or 75% dose reduction | 894 | 2 patients received normal doses. (no tox data reported) | n = 7761/13.6% | N = 22/22,7 | n = 34/23,5% | Pooled with heterozygous. n = 34/23,5% |
| Etienne‐Grimaldi 2017 (28481884) | Retrospective | No dose reduction | 243 | No dose intervention | n = 239/11.8% | No dose intervention | n = 11/45.5% | No patients found |
| Meulendijks 2016 (26804235) | Retrospective | No dose reduction | 1592 | No dose intervention | n = 1429/10% | No dose intervention | n = 79/14% (11/79) | No patients found |
| Froehlich 2015 (24923815) | Retrospective | No dose reduction | 500 | No dose intervention | All patients including DPYD‐variant carriers 14% | No dose intervention | n = 33/15.3% | No patients found |
| Shakeel 2021 (33410339) | Retrospective | No dose reduction | 582 | No dose intervention | n = 543/18.1% | No dose intervention | n = 39/36.5% | 2 patients. HapB3/HabB3 + *2A/HapB3 |
| Capitain 2020 (32973417) | Retrospective | No dose reduction | 472 | No dose intervention | n = 377/48% | No dose intervention | n = 90/89% | n = 5/100% (4 dead of tox. Last 1 grade 4) |
| Ruzzo 2017 (29065426) | Retrospective | No dose reduction | 508 | No dose intervention | ALL PATIENTS INCLUDING VARIANTS n = 508/38.2% | No dose intervention | DPYD *2A (HR 15.34, 4.72–49.89) D494V (HR 3.02, 1.12–8.16) HapB3 (HR 0.99 [0.37–2.6]) No DPYD*13 found | No patients found |
| Boige 2016 (26794347) | Retrospective | No dose reduction | 1545 | No dose intervention | ALL PATIENTS INCLUDING VARIANTSn = 1545/49.5% | No dose intervention | D949V (OR 6.3 [2–27]) DP YD*2A (OR 2.2[0.6–10]) DPYD*13 (OR 0.7 [0.079–6.2]) HapB3 (OR 1 [0.55–1.8]) | No patients found |
| DelRe 2019 (30723313) | Retrospective | No dose reduction | 1254 | No dose intervention | Comparison of two cohorts. Cohort 1(tox) (n = 982) grade 3 neutropenia 4.7% /Cohort 2 n = 272/0% tox | No dose intervention | *2A(Febrile neutropenia: OR 4.2, p < 0.5) D949V (diarrhoea: OR 2.78, p < 0.05) No DPYD*13 or HapB3 found | No patients found |
| Deenen 2011 (21498394) | Retrospective | No dose reduction | 568 | No dose intervention | ALL PATIENTS INCLUDING VARIANTS/n = 568/85% * Any (non)hematologic toxicity | No dose intervention | Any (non)hematologic toxicity: DPYD*13/n = 1/0% HabB3 n = 28 / 93% DPYD*2A n = 7/100% D949V n = 8/88% Total = 40/44/91% | Some for HapB3. Unknown number. Pooled with HapB3 heterzyous |
Abbreviations: DPYD, gene encoding dihydropyrimidine dehydrogenase; toxcity grading, Common Terminology Criteria for Adverse Events (CTCAE); [U], plasma uracil concentration; [UH2], plasma dihydrouracil concentration.