
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 Clin, 2021, 71(3): 209. |
2 | Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(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 Oncol, 2021, 13(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 Oncol, 2022, 40(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 Cancer, 2019, 18(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 Netw, 2020, 18(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 Cancer, 2022, 21(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 Oncol, 2021, 22(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 Oncol, 2023, 41(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 Oncol, 2002, 20(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 Oncol, 2007, 25(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 Rev, 2016, 48(4): 502. |
13 | Li M, Seiser EL, Baldwin RM, et al. ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia[J]. Pharmacogenomics J, 2018, 18(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 Pharmacol, 2016, 78(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 Genomics, 2007, 17(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 Cancer, 2010, 103(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 Oncol, 2017, 18(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 Res, 2014, 2(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 Invest, 2014, 124(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 Med, 2020, 26(4): 566. |
21 | Le DT, Uram JN, Wang H, et al. PD-1 Blockade in tumors with mismatch-repair deficiency[J]. N Engl J Med, 2015, 372(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 Oncol, 2020, 38(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, 2021, 24(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, 2022, 42(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 Oncol, 2021, 32(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 Oncol, 2021, 39(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 Cancer, 2021, 9(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 Oncol, 2020, 15(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 Oncol, 2021, 8(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, 2021, 24(6): 473. |
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.
","bibtexUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=BibTeX&id=703","abstractUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/10.3969/j.issn.2097-0005.2024.09.012","zuoZheCn_L":"李雨晴, 胡静, 钱晓萍","juanUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/Y2024","lanMu_en":"Review","qiUrl_en":"//www.pitakata.com/xuebao/EN/Y2024/V45/I9","zuoZhe_EN":"Yuqing LI1, Jing HU2, Xiaoping QIAN1,2(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.
Application of three-drug chemotherapy in neoadjuvant therapy for locally advanced rectal cancer
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.
three-drug chemotherapy/locally advanced/rectal cancer/neoadjuvant therapy
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 Clin,2021,71(3): 209. |
2 | Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J].CA Cancer J Clin,2022,72(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 Oncol,2021,13(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 Oncol,2022,40(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 Cancer,2019,18(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 Netw,2020,18(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 Cancer,2022,21(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 Oncol,2021,22(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 Oncol,2023,41(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 Oncol,2002,20(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 Oncol,2007,25(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 Rev,2016,48(4): 502. |
13 | Li M, Seiser EL, Baldwin RM, et al. ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia[J].Pharmacogenomics J,2018,18(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 Pharmacol,2016,78(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 Genomics,2007,17(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 Cancer,2010,103(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 Oncol,2017,18(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 Res,2014,2(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 Invest,2014,124(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 Med,2020,26(4): 566. |
21 | Le DT, Uram JN, Wang H, et al. PD-1 Blockade in tumors with mismatch-repair deficiency[J].N Engl J Med,2015,372(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 Oncol,2020,38(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,2021,24(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,2022,42(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 Oncol,2021,32(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 Oncol,2021,39(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 Cancer,2021,9(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 Oncol,2020,15(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 Oncol,2021,8(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,2021,24(6): 473. |
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