Relationship between UGT1A1*6/*28 polymorphisms and severe toxicities in Chinese patients with pancreatic or biliary tract cancer treated with irinotecan-containing regimens

Abstract

Chen Yang,1 Ying Liu,1 Wen-qi Xi,1 Chen-fei Zhou,2 Jin-ling Jiang,1 Tao Ma,1 Zheng-bao Ye,1 Jun Zhang,1 Zheng-gang Zhu1,2 1Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China Purpose: The aim of this retrospective study was to investigate the relationship between UGT1A1 polymorphisms and toxicities in Chinese patients with pancreatic or biliary tract cancer receiving irinotecan-containing regimens as the second- or third-line chemotherapy.Patients and methods: A total of 36 patients with unresectable pancreatic cancer and 12 patients with unresectable biliary tract cancer were included. Approximately 33 patients were treated with FOLFIRI regimen, a chemotherapy regimen, where FOL stands for folinic acid, F for fluorouracil, and IRI for irinotecan (irinotecan 180 mg/m2 at day 1, CF 200 mg/m2 at day 1–2, 5-FU 400 mg/m2 at day 1–2, followed by continuous infusion of 5-FU 600 mg/m2 for 22 hours at day 1–2, every 2 weeks). The other 15 patients were treated with irinotecan monotherapy (180 mg/m2, every 2 weeks). UGT1A1*6/*28 polymorphisms were detected by direct sequencing.Results: The frequencies of GG, GA, AA genotypes for UGT1A1*6 were 70.8% (n=34), 25.0% (n=12), and 4.2% (n=2), respectively. And those of TA6/TA6, TA6/TA7, TA7/TA7 for UGT1A1*28 were 79.2% (n=38), 18.8% (n=9), and 2.0% (n=1), respectively. A total of 22 patients (45.8%) had grade III–IV neutropenia, and six patients (12.5%) experienced grade III–IV diarrhea. The incidence of grade III–IV neutropenia in patients with UGT1A1*6 GA or AA genotype was 71.4%, which was significantly higher than that with GG genotype (35.3%, P=0.022). No relationship was found between grade III–IV neutropenia and UGT1A1*28 polymorphism. The statistical analysis between grade III–IV diarrhea and UGT1A1*6/*28 polymorphisms was not conducted in view of the limited number of patients.Conclusion: In Chinese patients with pancreatic or biliary tract cancer administered irinotecan-containing regimens, those with UGT1A1*6 variant may have a high risk of severe neutropenia. Keywords: UGT1A1 polymorphism, irinotecan, pancreatic cancer, biliary tract cancer, neutropenia, diarrhea