Implementing Pre-Therapeutic Genotyping in Clinical Practice: A Real-Life Study.

Current guidelines recommend pre-therapeutic 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 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 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 (OR = 0.38; 95% CI: 0.14-1.03; = 0.058), and in 15.3% of those receiving a reduced dose for clinical reasons (OR = 0.28, 95% IC: 0.12-0.67; = 0.004). Occurrence of severe neutropenia was inversely associated with dose reduction in homozygous carriers (OR = 0.62, 95% CI: 0.27-1.40, = 0.249) and heterozygous or wild-type patients (OR = 0.87, 95% CI: 0.59-1.28, = 0.478). Incidence of severe neutropenia was related to irinotecan doses and polymorphisms. Upfront irinotecan dose reductions do not reduce the burden of grade ≥ 3 neutropenia in homozygous carriers.