FOLFOXIRI Regimen for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Leal, Frederico; Ferreira, Fernanda Proa; Sasse, André Deeke

doi:10.1016/j.clcc.2017.03.012

Cited by 13 publications

(12 citation statements)

References 28 publications

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“…FOLFOXIRI remains the most applied and important first-line treatment of mCRC, further guiding treatment decisions [60]. Despite the existence of greater toxicity, it remains manageable [29]. The treatment with chemotherapy combination turns non-resectable aggressive tumors into resectable lesions and changes the molecular pattern of the tumor [9].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we analyzed the drug-drug interactions within the FA, 5-FU, OX, and SN (the active metabolite of IRI) combination (FA/5-FU/OX/SN) in human colorectal carcinoma cell lines. We chose the combination of FA/5-FU/OX/SN due to higher overall and progression-free survival in patients with mCRC, compared to standard chemotherapy regimens [20,29]. We used predefined matrices called 'orthogonal array composite designs' for experimental testing of multidrug combinations and a second-order linear regression model for data analysis [30].…”

Section: Introductionmentioning

confidence: 99%

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Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment

et al. 2020

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The combination of folinic acid, 5-fluorouracil, oxaliplatin and/or irinotecan (FOLFOXIRI) is the standard of care for metastatic colorectal cancer (CRC). This strategy inhibits tumor growth but provokes drug resistance and serious side effects. We aimed to improve FOLFOXIRI by optimization of the dosing and the sequence of drug administration. We employed an orthogonal array composite design and linear regression analysis to obtain cell line-specific drug combinations for four CRC cell lines (DLD1, SW620, HCT116, LS174T). Our results confirmed the synergy between folinic acid and 5-fluorouracil and additivity, or even antagonism, between the other drugs of the combination. The drug combination administered at clinical doses resulted in significantly higher antagonistic interactions compared to the low-dose optimized drug combination (ODC). We found that the concomitant administration of the optimized drug combination (ODC) was comparatively active to sequential administration. However, the administration of oxaliplatin or the active metabolite of irinotecan seemed to sensitize the cells to the combination of folinic acid and 5-fluorouracil. ODCs were similarly active in non-cancerous cells as compared to the clinically used doses, indicating a lack of reduction of side effects. Interestingly, ODCs were inactive in CRC cells chronically pretreated with FOLFOXIRI, suggesting the occurrence of resistance. We were unable to improve FOLFOXIRI in terms of efficacy or specificity. Improvement of CRC treatment should come from the optimization of targeted drugs and immunotherapy strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment

et al. 2020

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“…Irinotecan is a semi-synthetic derivative of natural camptothecin, and has been widely used in the treatment of solid tumors such as gastric cancer, colorectal cancer (CRC), lung cancer, etc. A combination of irinotecan and fluorouracil is a standard first-line regimen for advanced CRC, especially advanced CRC with rapid progression, with an efficacy rate of up to 40% [10][11][12]. However, this regimen has two major adverse reactions of delayed-onset diarrhea and neutropenia, where the incidences of grade 3~4 neutropenia and severe diarrhea are 45% and 20~40% [13], respectively, which limits its clinical application and exhibits inter-individual variations.…”

Section: Discussionmentioning

confidence: 99%

Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang

Chen

Feng

et al. 2020

BMC Gastroenterol

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Background: There are obviously ethnic differences between the UGT1A1 gene polymorphisms. Due to the difference of genetic background and environment, the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan-based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled. The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1*28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method.

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“…Combination therapy with more agents may be effective countermeasure to drug resistance due to tumor heterogeneity. In addition, the toxicity of triplet regimen is greater while anticancer effect of triplet is superior to doublet in CRC (27). Therefore, we designed chemoradiation with triplet radiosensitizer of fluoropyrimidines, oxaliplatin, and irinotecan and adopted a sequential schedule of oxaliplatin and irinotecan for low toxicity.…”

Section: Discussionmentioning

confidence: 99%

Phase�I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S‑1 for locally advanced rectal cancer

et al. 2019

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The present study designed a novel preoperative chemoradiotherapy (CRT) with sequential oxaliplatin and irinotecan with S-1 for locally advanced rectal cancer (LARC). This phase I study evaluated the maximum tolerated dose and recommended dose (RD) of oxaliplatin following irinotecan with S-1. Patients with clinical stage T3 or 4 or involvement of the regional nodes and no evidence of distant metastases were treated with fixed doses of S-1 (80 mg/m 2 /day) on days 1-5, 8-12, 15-19, 22-27 and 29-33, and irinotecan (40 mg/m 2 /day) on days 1 and 8, followed by oxaliplatin on days 22 and 29. The dose of oxaliplatin was initially 40 mg/m 2 (level 1) with a predefined dose escalation schedule. The radiation dose was 1.8 Gy/fraction to a total dose of 45 Gy. A total of 9 patients were enrolled in the present study and 7 patients completely received CRT with this study protocol. The maximum tolerated dose for oxaliplatin was 50 mg/m 2 (level 2). Three of four patients experienced dose-limiting toxicity (grade 3 diarrhea) in oxaliplatin phase of level 2 dose. The RD of oxaliplatin was 40 mg/m 2 (level 1 dose). In addition, 2 patients had pathological CR (28.5%). Novel preoperative CRT with sequential oxaliplatin and irinotecan with S-1 for LARC resulted in acceptable toxicity and promising efficacy. However, the RD of oxaliplatin was lower than in previous CRT studies that combined oxaliplatin with S-1. To administer higher oxaliplatin, we have planned a phase I trial of preoperative CRT with sequential oxaliplatin followed by irinotecan with S-1 for LARC.

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FOLFOXIRI Regimen for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Cited by 13 publications

References 28 publications

Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment

Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment

Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang

Phase�I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S‑1 for locally advanced rectal cancer

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