| Autor: |
Nicola Personeni, Laura Giordano, Angelica Michelini, Antonio D’Alessio, Antonella Cammarota, Silvia Bozzarelli, Tiziana Pressiani, Maria Giuseppina Prete, Maria Teresa Sandri, Sabine Stioui, Luca Germagnoli, Armando Santoro, Lorenza Rimassa, Rossana Mineri |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Journal of Personalized Medicine; Volume 12; Issue 2; Pages: 204 |
| ISSN: |
2075-4426 |
| DOI: |
10.3390/jpm12020204 |
| Popis: |
Current guidelines recommend pre-therapeutic UGT1A1 genotyping to guide irinotecan dosing, but the usefulness of this approach remains to be clarified. In 247 patients with advanced gastrointestinal cancers undergoing irinotecan-based chemotherapy, we prospectively performed UGT1A1*28 genotyping and we analyzed the incidence of severe neutropenia according to genotype-guided dose reductions. Overall, 28 (11.3%) and 92 (37.2%) patients were homozygous or heterozygous UGT1A1*28 carriers, respectively. Grade ≥ 3 neutropenia was reported in 39% of homozygous patients receiving an upfront dose reduction of irinotecan (median 40%, range 22–58%), in 20% of heterozygous or wild-type patients receiving full dose (ORvs*28/*28 genotype = 0.38; 95% CI: 0.14–1.03; p = 0.058), and in 15.3% of those receiving a reduced dose for clinical reasons (OR vs*28/*28 genotype = 0.28, 95% IC: 0.12–0.67; p = 0.004). Occurrence of severe neutropenia was inversely associated with dose reduction in UGT1A1*28 homozygous carriers (ORx10 unit = 0.62, 95% CI: 0.27–1.40, p = 0.249) and UGT1A1 heterozygous or wild-type patients (ORx10 unit = 0.87, 95% CI: 0.59–1.28, p = 0.478). Incidence of severe neutropenia was related to irinotecan doses and UGT1A1 polymorphisms. Upfront irinotecan dose reductions do not reduce the burden of grade ≥ 3 neutropenia in UGT1A1*28 homozygous carriers. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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