xiaopingqian@nju.edu.cn。
"],"authorList":[{"zuoZheDiZhiL_cn":["东南大学医学院,江苏 南京 210009 ;"],"deceased":false,"name_cn":"李雨晴","zuoZheDiZhiL_en":["Medical School of Southeast University,Nanjing 210009,China ;"],"name_en":"Yuqing LI"},{"zuoZheDiZhiL_cn":["南京大学医学院附属鼓楼医院肿瘤中心,江苏 南京 210008 ;"],"deceased":false,"name_cn":"胡静","zuoZheDiZhiL_en":["Comprehensive Cancer Center of Nanjing Drum Tower Hospital,Affiated Hospital of Medical School,Nanjing 210008,China ;"],"name_en":"Jing HU"},{"zuoZheDiZhiL_cn":["东南大学医学院,江苏 南京 210009 ;南京大学医学院附属鼓楼医院肿瘤中心,江苏 南京 210008 ;"],"deceased":false,"name_cn":"钱晓萍","email":"xiaopingqian@nju.edu.cn","zuoZheDiZhiL_en":["Medical School of Southeast University,Nanjing 210009,China ;Comprehensive Cancer Center of Nanjing Drum Tower Hospital,Affiated Hospital of Medical School,Nanjing 210008,China ;"],"name_en":"Xiaoping QIAN"}],"affList_en":["1.Medical School of Southeast University,Nanjing 210009,China
2.Comprehensive Cancer Center of Nanjing Drum Tower Hospital,Affiated Hospital of Medical School,Nanjing 210008,China"],"fundList_cn":["江苏省自然科学基金面上项目(BK20211007);江苏省中医药科技发展重点项目(ZD202227);南京市医学重点基金(ZKX21028)"],"affList_cn":["1.东南大学医学院,江苏 南京 210009
2.南京大学医学院附属鼓楼医院肿瘤中心,江苏 南京 210008"],"article":{"keywordList_cn":["三药化疗","局部进展期","直肠癌","新辅助治疗"],"juan":"45","zhaiyao_cn":"

目前局部进展期直肠癌(locally advanced rectal cancer,LARC)的标准治疗模式为新辅助放化疗联合直肠全系膜切除和辅助化疗,患者的生存预后显著改善,但远处转移率仍较高。既往常应用于新辅助治疗中的化疗方案为FOLFOX(奥沙利铂+氟尿嘧啶/亚叶酸钙)或FOLFIRI(伊立替康+氟尿嘧啶/亚叶酸钙)双药方案,而FOLFOXIRI(氟尿嘧啶/亚叶酸钙+奥沙利铂+伊立替康)三药方案强度更高,本文就三药化疗在LARC新辅助治疗中的应用展开综述,以期为临床诊疗提供参考。

","endNoteUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=EndNote&id=703","reference":"
1 Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin202171(3): 209.
2 Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin202272(1): 7.
3 Tuta M, Boc N, Brecelj E, et al. Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure[J]. World J Gastrointest Oncol202113(2): 119.
4 Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy[J]. J Clin Oncol202240(23): 2546.
5 Zhang JW, Huang MJ, Cai Y, et al. Neoadjuvant chemotherapy with mFOLFOXIRI without routine use of radiotherapy for locally advanced rectal cancer[J]. Clin Colorectal Cancer201918(4): 238.
6 Benson AB, Venook AP, Al-Hawary MM, et al. NCCN guidelines insights: rectal cancer, version 6.2020[J]. J Natl Compr Canc Netw202018(7): 806.
7 Ding MM, Zhang JW, Hu HB, et al. mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: a propensity score matching analysis[J]. Clin Colorectal Cancer202221(1): e12.
8 Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol202122(5): 702.
9 Conroy T, Etienne PL, Rio E, et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: 7-year results of PRODIGE 23 phase Ⅲ trial, a UNICANCER GI trial[J]. J Clin Oncol202341(17): LBA3504.
10 Falcone A, Masi G, Allegrini G, et al. Biweekly chemotherapy with oxaliplatin, irinotecan, infusional Fluorouracil, and leucovorin: a pilot study in patients with metastatic colorectal cancer[J]. J Clin Oncol200220(19): 4006.
11 Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest[J]. J Clin Oncol200725(13): 1670.
12 Chen S, Sutiman NTI, Zhang CZ, et al. Pharmacogenetics of irinotecan, doxorubicin and docetaxel transporters in Asian and Caucasian cancer patients: a comparative review[J]. Drug Metab Rev201648(4): 502.
13 Li M, Seiser EL, Baldwin RM, et al. ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia[J]. Pharmacogenomics J201818(1): 35.
14 Xu CL, Tang XS, Qu YL, et al. UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer[J]. Cancer Chemother Pharmacol201678(1): 119.
15 Minami H, Sai K, Saeki M, et al. Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28[J]. Pharmacogenet Genomics200717(7): 497.
16 Martinez-Balibrea E, Abad A, Martínez-Cardús A, et al. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy[J]. Br J Cancer2010103(4): 581.
17 Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study[J]. Lancet Oncol201718(9): 1182.
18 Tang C, Wang XH, Soh H, et al. Combining radiation and immunotherapy: a new systemic therapy for solid tumors?[J]. Cancer Immunol Res20142(9): 831.
19 Deng LF, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice[J]. J Clin Invest2014124(2): 687.
20 Chalabi M, Fanchi LF, Dijkstra KK, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers[J]. Nat Med202026(4): 566.
21 Le DT, Uram JN, Wang H, et al. PD-1 Blockade in tumors with mismatch-repair deficiency[J]. N Engl J Med2015372(26): 2509.
22 Yuki S, Bando H, Tsukada Y, et al. Short-term results of VOLTAGE-A: Nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer[J]. J Clin Oncol202038(15): 4100.
23 李英杰, 张丽, 董秋石, 等. 程序性细胞死亡蛋白1抗体联合全程新辅助放化疗治疗高风险局部进展期中低位直肠癌患者的近期结局[J]. 中华胃肠外科杂志202124(11): 998.
24 高加勒, 张潇, 杨正阳, 等. pMMR局部进展期中低位直肠癌行新辅助放化疗联合替雷利珠单克隆抗体的探索研究[J]. 中国实用外科杂志202242(8): 913.
25 Carrasco J, Schr?der D, Sinapi I, et al. 397P R-IMMUNE interim analysis: a phase Ib/Ⅱ study to evaluate safety and efficacy of atezolizumab combined with radio-chemotherapy in a preoperative setting for patients with localized rectal cancer[J]. Ann Oncol202132(S5): S537.
26 Salvatore L, Bensi M, Pietrantonio F, et al. Phase Ⅱ study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): the AVANA study[J]. J Clin Oncol202139(15): 3511.
27 LIN ZY, CAI M, ZHANG P,et al.Phase Ⅱ,single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer[J].J Immunother Cancer20219(11):1.
28 Shamseddine A, Zeidan YH, El Husseini Z, et al. Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma[J]. Radiat Oncol202015(1): 233.
29 Laengle J, Kuehrer I, Pils D, et al. Neoadjuvant chemoradiotherapy with sequential ipilimumab and nivolumab in rectal cancer (CHINOREC): a prospective randomized, open-label, multicenter, phase Ⅱ clinical trial[J]. J Clin Oncol20218(2): TPS3623.
30 中国南方肿瘤临床研究协会结直肠癌专业委员会. 结直肠癌改良三药cmFOLFOXIRI方案临床应用中国专家共识[J]. 中华胃肠外科杂志202124(6): 473.
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The standard treatment of locally advanced rectal cancer (LARC) is the mode of neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) plus adjuvant chemotherapy (ACT). Neoadjuvant therapy significantly improves prognosis. However, the rate of distant metastasis is still kept high. The usual neoadjuvant chemotherapy is FOLFOX or FOLFIRI two-drug regimens, while FOLFOXIRI three-drug regimen remains stronger. This article has summarized the application of three-drug chemotherapy in neoadjuvant therapy for LARC, hoping to provide reference for clinical diagnosis and treatment.

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Application of three-drug chemotherapy in neoadjuvant therapy for locally advanced rectal cancer

Yuqing LI, Jing HU, Xiaoping QIAN

Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences››2024, Vol. 45››Issue (9): 573-576.

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Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences ›› 2024, Vol. 45 ›› Issue (9) : 573-576. DOI: 10.3969/j.issn.2097-0005.2024.09.012
Review

Application of three-drug chemotherapy in neoadjuvant therapy for locally advanced rectal cancer

    Author information +
    History +

    Abstract

    The standard treatment of locally advanced rectal cancer (LARC) is the mode of neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) plus adjuvant chemotherapy (ACT). Neoadjuvant therapy significantly improves prognosis. However, the rate of distant metastasis is still kept high. The usual neoadjuvant chemotherapy is FOLFOX or FOLFIRI two-drug regimens, while FOLFOXIRI three-drug regimen remains stronger. This article has summarized the application of three-drug chemotherapy in neoadjuvant therapy for LARC, hoping to provide reference for clinical diagnosis and treatment.

    Key words

    three-drug chemotherapy/locally advanced/rectal cancer/neoadjuvant therapy

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    Yuqing LI, Jing HU, Xiaoping QIAN.Application of three-drug chemotherapy in neoadjuvant therapy for locally advanced rectal cancer[J]. Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences. 2024, 45(9): 573-576 https://doi.org/10.3969/j.issn.2097-0005.2024.09.012

    References

    1 Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin202171(3): 209.
    2 Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J].CA Cancer J Clin202272(1): 7.
    3 Tuta M, Boc N, Brecelj E, et al. Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure[J].World J Gastrointest Oncol202113(2): 119.
    4 Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy[J].J Clin Oncol202240(23): 2546.
    5 Zhang JW, Huang MJ, Cai Y, et al. Neoadjuvant chemotherapy with mFOLFOXIRI without routine use of radiotherapy for locally advanced rectal cancer[J].Clin Colorectal Cancer201918(4): 238.
    6 Benson AB, Venook AP, Al-Hawary MM, et al. NCCN guidelines insights: rectal cancer, version 6.2020[J].J Natl Compr Canc Netw202018(7): 806.
    7 Ding MM, Zhang JW, Hu HB, et al. mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: a propensity score matching analysis[J].Clin Colorectal Cancer202221(1): e12.
    8 Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial[J].Lancet Oncol202122(5): 702.
    9 Conroy T, Etienne PL, Rio E, et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: 7-year results of PRODIGE 23 phase Ⅲ trial, a UNICANCER GI trial[J].J Clin Oncol202341(17): LBA3504.
    10 Falcone A, Masi G, Allegrini G, et al. Biweekly chemotherapy with oxaliplatin, irinotecan, infusional Fluorouracil, and leucovorin: a pilot study in patients with metastatic colorectal cancer[J].J Clin Oncol200220(19): 4006.
    11 Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest[J].J Clin Oncol200725(13): 1670.
    12 Chen S, Sutiman NTI, Zhang CZ, et al. Pharmacogenetics of irinotecan, doxorubicin and docetaxel transporters in Asian and Caucasian cancer patients: a comparative review[J].Drug Metab Rev201648(4): 502.
    13 Li M, Seiser EL, Baldwin RM, et al. ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia[J].Pharmacogenomics J201818(1): 35.
    14 Xu CL, Tang XS, Qu YL, et al. UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer[J].Cancer Chemother Pharmacol201678(1): 119.
    15 Minami H, Sai K, Saeki M, et al. Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28[J].Pharmacogenet Genomics200717(7): 497.
    16 Martinez-Balibrea E, Abad A, Martínez-Cardús A, et al. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy[J].Br J Cancer2010103(4): 581.
    17 Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study[J].Lancet Oncol201718(9): 1182.
    18 Tang C, Wang XH, Soh H, et al. Combining radiation and immunotherapy: a new systemic therapy for solid tumors?[J].Cancer Immunol Res20142(9): 831.
    19 Deng LF, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice[J].J Clin Invest2014124(2): 687.
    20 Chalabi M, Fanchi LF, Dijkstra KK, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers[J].Nat Med202026(4): 566.
    21 Le DT, Uram JN, Wang H, et al. PD-1 Blockade in tumors with mismatch-repair deficiency[J].N Engl J Med2015372(26): 2509.
    22 Yuki S, Bando H, Tsukada Y, et al. Short-term results of VOLTAGE-A: Nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer[J].J Clin Oncol202038(15): 4100.
    23 李英杰, 张丽, 董秋石, 等. 程序性细胞死亡蛋白1抗体联合全程新辅助放化疗治疗高风险局部进展期中低位直肠癌患者的近期结局[J].中华胃肠外科杂志202124(11): 998.
    24 高加勒, 张潇, 杨正阳, 等. pMMR局部进展期中低位直肠癌行新辅助放化疗联合替雷利珠单克隆抗体的探索研究[J].中国实用外科杂志202242(8): 913.
    25 Carrasco J, Schr?der D, Sinapi I, et al. 397P R-IMMUNE interim analysis: a phase Ib/Ⅱ study to evaluate safety and efficacy of atezolizumab combined with radio-chemotherapy in a preoperative setting for patients with localized rectal cancer[J].Ann Oncol202132(S5): S537.
    26 Salvatore L, Bensi M, Pietrantonio F, et al. Phase Ⅱ study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): the AVANA study[J].J Clin Oncol202139(15): 3511.
    27 LIN ZY, CAI M, ZHANG P,et al.Phase Ⅱ,single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer[J].J Immunother Cancer20219(11):1.
    28 Shamseddine A, Zeidan YH, El Husseini Z, et al. Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma[J].Radiat Oncol202015(1): 233.
    29 Laengle J, Kuehrer I, Pils D, et al. Neoadjuvant chemoradiotherapy with sequential ipilimumab and nivolumab in rectal cancer (CHINOREC): a prospective randomized, open-label, multicenter, phase Ⅱ clinical trial[J].J Clin Oncol20218(2): TPS3623.
    30 中国南方肿瘤临床研究协会结直肠癌专业委员会. 结直肠癌改良三药cmFOLFOXIRI方案临床应用中国专家共识[J].中华胃肠外科杂志202124(6): 473.
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