PMID- 37201062 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230521 IS - 2078-6891 (Print) IS - 2219-679X (Electronic) IS - 2078-6891 (Linking) VI - 14 IP - 2 DP - 2023 Apr 29 TI - A single-center retrospective analysis of the efficacy and safety of a modified regimen of irinotecan plus S-1 (IRIS) with molecular targeting agents as second-line chemotherapy in Japanese patients with recurrent or nonresectable colorectal cancer. PG - 663-675 LID - 10.21037/jgo-22-899 [doi] AB - BACKGROUND: As the second-line chemotherapy for stage IV recurrent or nonresectable colorectal cancer, our hospital started a modified treatment regimen comprising of irinotecan plus S-1 (IRIS) [tegafur/gimeracil/oteracil (S-1)] plus molecular targeting agents (MTAs), i.e., an epidermal growth factor receptor (EGFR) inhibitor such as panitumumab (P-mab) or cetuximab (C-mab) or vascular endothelial growth factor (VEGF) inhibitor such as bevacizumab (B-mab) since October 2012. The purpose of this study is to evaluate the efficacy and safety of this modified regimen. METHODS: This retrospective study included 41 patients with advanced recurrent colorectal cancer at our hospital whom at least 3 courses of chemotherapy were conducted from January 2015 to December 2021. Based on the location of the primary tumor, patients were classified into two group (right-sided group, proximal to the splenic curve, and left-sided, distal to the splenic curve). We assessed archived data on RAS and BRAF status and UGT1A1 polymorphisms and use of the VEGF inhibitor bevacizumab (B-mab) and the EGFR inhibitors panitumumab (P-mab) and cetuximab (C-mab). In addition, progression-free survival rate (36M-PFS) and the overall survival rate (36M-OS) were calculated. Furthermore, the respective median survival time (MST), the median number of treatment courses; the objective response rate (ORR) and clinical benefit rate (CBR) and the incidence of adverse events (AEs) were assessed as well. RESULTS: There were 11 patients (26.8%) in the right-sided group, and 30 patients (73.2%) in the left-sided group. There were 19 patients with RAS wild type (46.3%) (1 in the right sided group and 18 in the left sided group). P-mab was used for 16 of these patients (84.2%), C-mab for 2 (10.5%), and B-mab for 1 (5.3%); the remaining 22 patients (53.7%). Ten patients in the right group and 12 patients in the left group were a mutated type and received B-mab. BRAF testing was performed in 17 patients (41.5%); as more than 50% of patients (58.5%) were included before the assay's introduction. Five patients in the right-sided group and 12 patients in the left-sided group had wild type. There was no mutated type. UGT1A1 polymorphism was tested in 16/41 patients: Eight were wild type (8/41 patients, 19.5%) and 8, mutated type. Regarding the *6/*28 double heterozygous type, there was only 1 patient in the right-sided group and the remaining 7 patients were in the left-sided group. The total number of chemotherapy courses was 299, and the median number, 6.0 (range, 3-20). PFS, OS, and MST were as follows: 36M-PFS (total/Rt/Lt), 6.2%/0.0%/8.5% (MST; 7.6/6.3/8.9 months); and 36M-OS (total/Rt/Lt), 32.1%/0.0%/44.0% (MST; 22.1/18.8/28.6 months). The ORR and CBR were 24.4% and 75.6%, respectively. The majority of AEs were grades 1 or 2 and were improved with conservative treatment. Grade 3 leukopenia was observed in 2 cases (4.9%), neutropenia in 4 cases (9.8%), and malaise/nausea/diarrhea/perforation in 1 case each (2.4%). Grade 3 leukopenia (2 patients) and neutropenia (3 patients) were more commonly observed in the left-sided group. Diarrhea and perforation were also common in the left-sided group. CONCLUSIONS: This second-line modified IRIS regimen with MTAs is safe and effective and results in good PFS and OS. CI - 2023 Journal of Gastrointestinal Oncology. All rights reserved. FAU - Higami, Shigeo AU - Higami S AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Mukai, Masaya AU - Mukai M AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Yokoyama, Daiki AU - Yokoyama D AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Uda, Syuji AU - Uda S AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Abe, Rin AU - Abe R AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Mamuro, Nana AU - Mamuro N AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Kishima, Kyoko AU - Kishima K AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Hasegawa, Sayuri AU - Hasegawa S AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Tajima, Takayuki AU - Tajima T AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Nomura, Eiji AU - Nomura E AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. FAU - Makuuchi, Hiroyasu AU - Makuuchi H AD - Department of Surgery, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20230410 PL - China TA - J Gastrointest Oncol JT - Journal of gastrointestinal oncology JID - 101557751 PMC - PMC10186548 OTO - NOTNLM OT - Colorectal cancer OT - chemotherapy OT - irinotecan plus S-1 (IRIS) OT - molecular targeting therapy OT - recurrent/non-resectable cancer COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-899/coif). The authors have no conflicts of interest to declare. EDAT- 2023/05/18 19:12 MHDA- 2023/05/18 19:13 PMCR- 2023/04/29 CRDT- 2023/05/18 16:54 PHST- 2022/09/17 00:00 [received] PHST- 2023/03/21 00:00 [accepted] PHST- 2023/05/18 19:13 [medline] PHST- 2023/05/18 19:12 [pubmed] PHST- 2023/05/18 16:54 [entrez] PHST- 2023/04/29 00:00 [pmc-release] AID - jgo-14-02-663 [pii] AID - 10.21037/jgo-22-899 [doi] PST - ppublish SO - J Gastrointest Oncol. 2023 Apr 29;14(2):663-675. doi: 10.21037/jgo-22-899. Epub 2023 Apr 10.