PMID- 35069808 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220430 IS - 1758-8340 (Print) IS - 1758-8359 (Electronic) IS - 1758-8340 (Linking) VI - 14 DP - 2022 TI - FOLFIRI (folinic acid, fluorouracil, and irinotecan) increases not efficacy but toxicity compared with single-agent irinotecan as a second-line treatment in metastatic colorectal cancer patients: a randomized clinical trial. PG - 17588359211068737 LID - 10.1177/17588359211068737 [doi] LID - 17588359211068737 AB - BACKGROUND: FOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC. METHODS: This randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis. RESULTS: A total of 172 patients with mCRC were randomly treated with FOLFIRI (n = 88) or irinotecan (n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911-1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3-4 neutropenia (47.7% versus 21.7%). CONCLUSION: This is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764. CI - (c) The Author(s), 2022. FAU - Zhang, Xiaowei AU - Zhang X AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Duan, Ran AU - Duan R AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Wang, Yusheng AU - Wang Y AD - Shanxi Tumor Hospital, Taiyuan, China. FAU - Liu, Xin AU - Liu X AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Zhang, Wen AU - Zhang W AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Zhu, Xiaodong AU - Zhu X AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Chen, Zhiyu AU - Chen Z AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Shen, Wei AU - Shen W AD - Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - He, Yifu AU - He Y AD - Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China. FAU - Wang, Hong Qiang AU - Wang HQ AD - Department of Oncology, Zhejiang Province Zhoushan Hospital, Zhoushan, China. FAU - Huang, Mingzhu AU - Huang M AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Wang, Chenchen AU - Wang C AUID- ORCID: 0000-0003-4930-3187 AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Zhang, Zhe AU - Zhang Z AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Zhao, Xiaoying AU - Zhao X AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Qiu, Lixin AU - Qiu L AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Luo, Jianfeng AU - Luo J AD - Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. FAU - Sheng, Xuedan AU - Sheng X AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Guo, Weijian AU - Guo W AD - Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. LA - eng SI - ClinicalTrials.gov/NCT02935764 PT - Journal Article DEP - 20220113 PL - England TA - Ther Adv Med Oncol JT - Therapeutic advances in medical oncology JID - 101510808 PMC - PMC8771434 OTO - NOTNLM OT - FOLFIRI OT - chemotherapy OT - irinotecan OT - metastatic colorectal cancer COIS- Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2022/01/25 06:00 MHDA- 2022/01/25 06:01 PMCR- 2022/01/13 CRDT- 2022/01/24 08:50 PHST- 2021/07/10 00:00 [received] PHST- 2021/12/02 00:00 [accepted] PHST- 2022/01/24 08:50 [entrez] PHST- 2022/01/25 06:00 [pubmed] PHST- 2022/01/25 06:01 [medline] PHST- 2022/01/13 00:00 [pmc-release] AID - 10.1177_17588359211068737 [pii] AID - 10.1177/17588359211068737 [doi] PST - epublish SO - Ther Adv Med Oncol. 2022 Jan 13;14:17588359211068737. doi: 10.1177/17588359211068737. eCollection 2022.