Evaluation of severe neutropenia and diarrhea in Asian cancer patients receiving UGT1A1 genotype-guided irinotecan dosing.

e13572 Background: Inactivation of SN-38, the active metabolite of irinotecan, occurs mainly via glucuronidation mediated by UDP glucuronosyltransferase (UGT) 1A1. The role of UGT1A1*6 and *28 polymorphisms in altering SN-38 disposition and increasing the risks of neutropenia and diarrhea has been reported in Asian cancer patients receiving standard-dose irinotecan. This study aimed to evaluate the incidence of severe neutropenia and diarrhea in Asian cancer patients treated with UGT1A1 genotype-guided doses of irinotecan. Methods: High Resolution Melting analysis was performed for the detection of UGT1A1*6 and *28 in 61 patients with advanced solid tumours prior to the initiation of irinotecan-based regimens. Irinotecan dose was administered according to their UGT1A1 genotypes and chemotherapy regimens. Incidence and severity of neutropenia and diarrhea were retrospectively evaluated over the entire duration of irinotecan therapy according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0. Results: Median age of the patients was 64 (range: 29 - 80). Majority of the patients were Chinese (77.0%), followed by Malays (14.8%) and Indians (8.2%). Of the 15 patients receiving single-agent irinotecan, only one (6.67%) developed grade 3/4 neutropenia and diarrhea. Two of the 19 patients (10.5%) treated with weekly XELIRI developed grade 3/4 neutropenia and none developed severe diarrhea. One of the 9 patients (11.1%) treated with three-weekly XELIRI developed grade 3/4 diarrhea and none developed grade 3/4 neutropenia. Three of the 10 patients (30.0%) treated with FOLFIRI had grade 3/4 neutropenia and one (10%) developed grade 3 diarrhea. Of the 6 patients treated with irinotecan and cisplatin, two patients (33.3%) developed grade 3/4 neutropenia and one patient (16.7%) developed grade 3/4 diarrhea. Both patients receiving irinotecan and 5-fluorouracil did not experience neutropenia and diarrhea. Conclusions: UGT1A1*6 and *28 genotype-guided dosing of irinotecan markedly reduced the incidence of grade 3/4 neutropenia and diarrhea in Asian cancer patients.