PMID- 26692528 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151222 LR - 20201001 IS - 1936-5233 (Print) IS - 1936-5233 (Electronic) IS - 1936-5233 (Linking) VI - 8 IP - 6 DP - 2015 Dec TI - 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. PG - 474-9 LID - S1936-5233(15)30011-5 [pii] LID - 10.1016/j.tranon.2015.11.002 [doi] AB - PURPOSE: 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. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Lu, Chien-Yu AU - Lu CY AD - 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. FAU - Huang, Ching-Wen AU - Huang CW AD - 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. FAU - Wu, I-Chen AU - Wu IC AD - 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. FAU - Tsai, Hsiang-Lin AU - Tsai HL AD - 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. FAU - Ma, Cheng-Jen AU - Ma CJ AD - Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Yeh, Yung-Sung AU - Yeh YS AD - 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. FAU - Chang, Se-Fen AU - Chang SF AD - Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Huang, Meng-Lin AU - Huang ML AD - Division of Colorectal Surgery, Department of Surgery, ZuoYing Armed Forces General Hospital, Kaohsiung, Taiwan. Electronic address: gis1253@gmail.com. FAU - Wang, Jaw-Yuan AU - Wang JY AD - 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. LA - eng PT - Journal Article PL - United States TA - Transl Oncol JT - Translational oncology JID - 101472619 PMC - PMC4700286 EDAT- 2015/12/23 06:00 MHDA- 2015/12/23 06:01 PMCR- 2015/12/12 CRDT- 2015/12/23 06:00 PHST- 2015/08/31 00:00 [received] PHST- 2015/11/01 00:00 [revised] PHST- 2015/11/02 00:00 [accepted] PHST- 2015/12/23 06:00 [entrez] PHST- 2015/12/23 06:00 [pubmed] PHST- 2015/12/23 06:01 [medline] PHST- 2015/12/12 00:00 [pmc-release] AID - S1936-5233(15)30011-5 [pii] AID - 10.1016/j.tranon.2015.11.002 [doi] PST - ppublish SO - Transl Oncol. 2015 Dec;8(6):474-9. doi: 10.1016/j.tranon.2015.11.002.