PMID- 33777142 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220421 IS - 1687-8450 (Print) IS - 1687-8469 (Electronic) IS - 1687-8450 (Linking) VI - 2021 DP - 2021 TI - UGT1A1 Polymorphism for Irinotecan Dose Escalation in Patients with BRAF-Mutated Metastatic Colorectal Cancer Treated with First-Line Bevacizumab and FOLFIRI. PG - 6686517 LID - 10.1155/2021/6686517 [doi] LID - 6686517 AB - BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and BRAF V600E mutation have a poor prognosis, with a median progression-free survival (PFS) of only 5-7 months after initial therapy. The current standard first-line chemotherapy for these patients includes FOLFOX or FOLFIRI plus bevacizumab. In this study, we explored the effects and oncological outcomes of UGT1A1 polymorphism for irinotecan escalation in patients with BRAF-mutated mCRC. Patients and Methods. This retrospective study included 17 patients with BRAF-mutated mCRC between April 2016 and December 2019. UGT1A1 genotyping was performed on all patients prior to initiating bevacizumab plus FOLFIRI chemotherapy. The primary endpoint was PFS, and the secondary endpoints were toxicity, response rate, disease control rate, and overall survival (OS). RESULTS: Fifteen and two patients had UGT1A1 1 */1 * and 1 */28 *, respectively. Eight underwent irinotecan dose escalation with tolerable adverse effects (AEs), and nine maintained an irinotecan dose of 180 mg/m(2) or required deescalation to 150 mg/m(2) due to intolerable AEs. After a median follow-up period of 15.7 (range, 3-54) months, the median PFS and OS were 9.4 and 15.7 months, respectively. Grade 3/4 AEs were observed in three (6%) patients. The disease control and partial response rates were 64.7% and 11.8%, respectively, indicating that most patients (14, 82.3%) could maintain this as a first-line line therapy with stable disease or proceed to second-line therapy if disease progression occurred, thereby maintaining acceptable performance status. CONCLUSIONS: The oncological outcomes of patients with BRAF-mutated mCRC treated using FOLFIRI plus bevacizumab with irinotecan dose escalation as a first-line therapy are acceptable with tolerable AEs; this may be a feasible treatment option in such patients. Pretherapeutic UGT1A1 genotyping-guided dose adjustment can achieve favorable outcomes. CI - Copyright (c) 2021 Yi-Chien Hsieh et al. FAU - Hsieh, Yi-Chien AU - Hsieh YC AUID- ORCID: 0000-0002-1474-6765 AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chang, Tsung-Kun AU - Chang TK AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Su, Wei-Chih AU - Su WC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Huang, Ching-Wen AU - Huang CW AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Tsai, Hsiang-Lin AU - Tsai HL AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chen, Yen-Cheng AU - Chen YC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Li, Ching-Chun AU - Li CC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chen, Po-Jung AU - Chen PJ AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung, Taiwan. FAU - Yin, Tzu-Chieh AU - Yin TC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Department of Surgery, Kaohsiung Municipal Tatung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Ma, Cheng-Jen AU - Ma CJ AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Division of Digestive and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Wang, Jaw-Yuan AU - Wang JY AUID- ORCID: 0000-0002-7705-2621 AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. LA - eng PT - Journal Article DEP - 20210309 PL - Egypt TA - J Oncol JT - Journal of oncology JID - 101496537 PMC - PMC7972843 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. EDAT- 2021/03/30 06:00 MHDA- 2021/03/30 06:01 PMCR- 2021/03/09 CRDT- 2021/03/29 06:25 PHST- 2020/11/15 00:00 [received] PHST- 2021/02/12 00:00 [revised] PHST- 2021/02/25 00:00 [accepted] PHST- 2021/03/29 06:25 [entrez] PHST- 2021/03/30 06:00 [pubmed] PHST- 2021/03/30 06:01 [medline] PHST- 2021/03/09 00:00 [pmc-release] AID - 10.1155/2021/6686517 [doi] PST - epublish SO - J Oncol. 2021 Mar 9;2021:6686517. doi: 10.1155/2021/6686517. eCollection 2021.