title: Clinical Implication of UGT1A1 Promoter Polymorphism for Irinotecan Dose Escalation in Metastatic Colorectal Cancer Patients Treated with Bevacizumab Combined with FOLFIRI in the First-line Setting.
abstract: OBJECTIVE
  This study aimed to identify the efficacy and toxicity of the FOLFIRI regimen (fluorouracil, leucovorin, and irinotecan) with irinotecan dose escalation plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC) via UGT1A1 genotyping.
  
  
  METHODS
  We administered bevacizumab plus FOLFIRI with irinotecan dose escalation to treat 70 mCRC patients. The UGT1A1 *1/*1 and *1/*28 genotypes started with a 180-mg/m(2) dose of irinotecan, and UGT1A1 *28/*28 genotype started with a dose of 120 mg/m(2). The dose of irinotecan was escalated at increasing intervals of 20 to 30 mg/m(2) until grade 3/4 adverse events (AEs) occurred. The clinical response rate, toxicity, and survival were analyzed.
  
  
  RESULTS
  The clinical response and disease control rates of mCRC patients treated with FOLFIRI plus bevacizumab were significantly better in patients with UGT1A1 *1/*1 and *1/*28 genotypes than in patients with UGT1A1 *28/*28 (P = .006 and P < .001, respectively). Grade 3/4 AEs were significantly more common in mCRC patients with the UGT1A1 *28/*28 genotype (P < .001). Progression-free survival was significantly higher in UGT1A1 *1/*1 and *1/*28 patients (P = .002). mCRC patients who underwent metastasectomy achieved better overall survival than those who did not undergo metastasectomy (P = .015).
  
  
  CONCLUSIONS
  Our study showed that mCRC patients with UGT1A1 *1/*1 and *1/*28 genotypes could receive escalated doses of irinotecan to obtain a more favorable clinical outcome without significant AEs.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Program of Bachelor of Health Beauty, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Cheng-Jen
authors.initials: CJ
authors.lastname: Ma
authors.affiliation: Division of Trauma, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yung-Sung
authors.initials: YS
authors.lastname: Yeh
authors.affiliation: Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Se-Fen
authors.initials: SF
authors.lastname: Chang
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, ZuoYing Armed Forces General Hospital, Kaohsiung, Taiwan. Electronic address: gis1253@gmail.com.
authors.forename: Meng-Lin
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Genomic Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung. Electronic address: cy614112@ms14.hinet.net.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang