Modified FOLFIRINOX in pancreatic cancer patients with double variant type of UGT1A1 polymorphism

Abstract

Background: UGT1A1 *28 or *6 polymorphism is associated with reduced enzyme activity and severe toxicity of irinotecan (CPT‐11), especially in patients homozygous for UGT1A1*28 or *6 and heterozygous for both UGT1A1*28 and *6 (double‐variant‐type: DV). FOLFIRINOX (FFX) is regarded as one of the standard treatments in patients with advanced pancreatic cancer (APC). The full‐dose regimen of FFX is not recommended in patients with UGT1A1 DV, but appropriate dose adjustment for such patients is not established yet. The purpose of this study was to evaluate the safety and efficacy of modified FFX (mFFX) for patients with DV as compared to patients without DV. Method: APC patients treated with mFFX from December 2013 to June 2014 at National Cancer Center Hospital East were enrolled. The mFFX regimen consisted of elimination of bolus 5‐FU and reduction of the CPT‐11 dose to 150mg/m2 for patients without UGT1A1 DV (non‐DV group) or 90‐100mg/m2 for patients with UGT1A1 DV (DV group).We retrospectively compared its safety and efficacy in the DV and non‐DV groups. Result: A total of 101 patients were enrolled, including 6 patients (6%) with DV. There were no significant differences in the baseline characteristics between the non‐DV and DV groups [median age in yr (65 vs. 63), PS 0 (66 vs. 50%), metastatic disease (87 vs. 100%), receiving mFFX as first‐line treatment (72 vs. 50%)]. Grade 3 or 4 adverse events in the Non‐DV and DV groups included neutropenia (44 vs. 50%), thrombocytopenia (3 vs. 0%), febrile neutropenia (7 vs. 16%), and diarrhea (3 vs. 16%). The differences in the toxicities were not statistically significant. The response rate (RR) and disease control rate (DCR) in the Non‐DV and DV groups were 24 vs. 17% and 83 vs. 83%, respectively. Conclusion: No significant differences in the incidence of adverse events, RR or DCR in response to mFFX were observed between APC Non‐DV patients receiving 150 mg/ m2 and APC DV patients receiving 90‐100 mg /m2 of CPT‐11.