FOLFIRINOX in advanced pancreatic cancer patients with the double-variant type of UGT1A1 polymorphism: A multicenter, retrospective study.

Abstract

484 Background: UGT1A1 *28 or *6 polymorphism is associated with reduced enzyme activity and severe toxicity of irinotecan, especially in patients homozygous for UGT1A1*28 or *6 and heterozygous for both UGT1A1*28 and *6 (double-variant-type: DV). FOLFIRINOX (FFX) is one of the standard treatments in patients with advanced pancreatic cancer (APC). In Japanese guideline for FFX in patients with APC, full-dose regimen of FFX is not recommended in patients with DV, but dose adjustment for patients with DV is not established yet. The purpose of this study was to evaluate the safety and efficacy of FFX in Japanese APC patients with DV. Methods: APC patient of DV treated with FFX from December 2013 to March 2016 in 16 hospitals in Japan were enrolled. Results: A total of 31 patients were enrolled. Irinotecan were variously administered at the first cycle of dose ranged from 70 to 180mg/m2. The proportion of the patients receiving standard dose of oxaliplatin, 5-FU infusion and 5-FU continuous infusion at the first cycle of FFX were 97%, 19% and 97%, respectively. Severe adverse events were observed 8 of 31 patients. Main grade 3 or 4 adverse events were included neutropenia (65%), febrile neutropenia (13%) and diarrhea (6%). Response rate (RR) and overall survival (OS) receiving FFX as first-line treatment were 23% and 13.5 months, respectively. In this study, patients receiving irinotecan 150mg/m2 was high frequency of 80% (4/5), otherwise, grade 4 neutropenia in all patients was observed in 29% (9/31) Conclusions: The results of neutropenia in this study indicated that irinotecan 150mg/m2 may not be tolerable in DV patients. RR and OS were almost the same as previous reports. We are planning the dose finding study of FFX in APC patients with DV.