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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Clinical Trial

同步放化疗联合尼莫单抗治疗老年食管鳞状细胞癌的疗效和安全性:一项前瞻性现实世界的实用研究

卷 23, 期 8, 2023

发表于: 27 April, 2023

页: [653 - 662] 页: 10

弟呕挨: 10.2174/1568009623666230315145937

价格: $65

Open Access Journals Promotions 2
摘要

背景:同步或最终放化疗是局部晚期食管鳞状细胞癌(ESCC)的标准治疗。老年患者因身体虚弱及多重合并症不能耐受标准同期化疗,接受放疗治疗。 目的:研究了同步(化疗)放疗联合尼莫单抗治疗老年ESCC患者的疗效和安全性。 方法; 符合条件的老年(≥70岁)局部晚期ESCC患者被纳入这项前瞻性、现实世界的实用研究,并接受同步放化疗或放疗联合尼莫单抗。主要终点是总生存期(OS)。次要终点为客观缓解率、疾病控制率、无进展生存期(PFS)和药物不良反应。 结果:纳入了53名老年患者。放疗联合尼莫单抗(RT+N) 32例(60.4%),同步放化疗联合尼莫单抗(CRT+N) 21例(39.6%)。中位年龄为75.8岁。14例(56.0%)患者获得部分缓解,11例(44.0%)患者在3个月时病情稳定。中位随访时间为24.4个月(95%CI, 21.6-26.7)个月。中位OS (mOS)为27.0 (95%CI, 14.8-48.4)个月。中位PFS (mPFS)为22.6个月(95%CI, 12.4-未达到)。更高的mPFS(未达到vs. 12.0个月;p=0.022)和mOS (48.4 vs 15.3个月;p=0.009),与RT+N组比较,CRT+N组有显著性差异。不良反应以1 ~ 2级为主(46.6%,86.8%)。 结论:在局部晚期ESCC老年患者中,同步放化疗或放疗联合尼莫单抗是安全且耐受性良好的。接受CRT+N治疗的ESCC患者寿命更长。

关键词: ESCC,尼莫单抗,老年患者,放化疗,总生存期,无进展生存期。

图形摘要
[1]
Zhang, S.; Sun, K.; Zheng, R.; Zeng, H.; He, J. Carcinoma incidence and mortality in China, 2015. J. Nat. Cancer. Cent., 2021, 1(1), 2-11.
[2]
Zeng, H.; Chen, W.; Zheng, R.; Zhang, S.; Ji, J.S.; Zou, X.; Xia, C.; Sun, K.; Yang, Z.; Li, H.; Wang, N.; Han, R.; Liu, S.; Li, H.; Mu, H.; He, Y.; Xu, Y.; Fu, Z.; Zhou, Y.; Jiang, J.; Yang, Y.; Chen, J.; Wei, K.; Fan, D.; Wang, J.; Fu, F.; Zhao, D.; Song, G.; Chen, J.; Jiang, C.; Zhou, X.; Gu, X.; Jin, F.; Li, Q.; Li, Y.; Wu, T.; Yan, C.; Dong, J.; Hua, Z.; Baade, P.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Changing cancer survival in China during 2003-15: A pooled analysis of 17 population-based cancer registries. Lancet Glob. Health, 2018, 6(5), e555-e567.
[http://dx.doi.org/10.1016/S2214-109X(18)30127-X] [PMID: 29653628]
[3]
Cao, X.; Sun, X. Incidence and trend of esophageal carcinoma. Chin. J. Clin. Oncol., 2016, 43(21), 932-936.
[4]
Feng, R.M.; Zong, Y.N.; Cao, S.M.; Xu, R.H. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics? Cancer Commun., 2019, 39(1), 22.
[http://dx.doi.org/10.1186/s40880-019-0368-6] [PMID: 31030667]
[5]
Jiang, D.; Li, X.; Wang, H.; Shi, Y.; Xu, C.; Lu, S.; Huang, J.; Xu, Y.; Zeng, H.; Su, J.; Hou, Y.; Tan, L. The prognostic value of EGFR overexpression and amplification in Esophageal squamous cell Carcinoma. BMC Cancer, 2015, 15(1), 377.
[http://dx.doi.org/10.1186/s12885-015-1393-8] [PMID: 25953424]
[6]
Wang, Y.; Yuan, Y.; Luo, X.; Hu, G.; Gong, P. Genetic variants in EGFR/PLCE1 pathway are associated with prognosis of esophageal squamous cell carcinoma after radical resection. Curr. Med. Sci., 2019, 39(3), 385-390.
[http://dx.doi.org/10.1007/s11596-019-2047-x] [PMID: 31209807]
[7]
Wang, J.; Yu, J.M.; Jing, S.W.; Guo, Y.; Wu, Y.J.; Li, N.; Jiao, W.P.; Wang, L.; Zhang, Y.J. Relationship between EGFR over-expression and clinicopathologic characteristics in squamous cell carcinoma of the esophagus: A meta-analysis. Asian Pac. J. Cancer Prev., 2014, 15(14), 5889-5893.
[http://dx.doi.org/10.7314/APJCP.2014.15.14.5889] [PMID: 25081654]
[8]
Saumell, Y.; Sanchez, L.; González, S.; Ortiz, R.; Medina, E.; Galán, Y.; Lage, A. Overall survival of patients with locally advanced or metastatic esophageal squamous cell carcinoma treated with nimotuzumab in the real world. Adv. Ther., 2017, 34(12), 2638-2647.
[http://dx.doi.org/10.1007/s12325-017-0631-7] [PMID: 29134427]
[9]
Mazorra, Z.; Chao, L.; Lavastida, A.; Sanchez, B.; Ramos, M.; Iznaga, N.; Crombet, T. Nimotuzumab: Beyond the EGFR signaling cascade inhibition. Semin. Oncol., 2018, 45(1-2), 18-26.
[http://dx.doi.org/10.1053/j.seminoncol.2018.04.008] [PMID: 30318080]
[10]
Takeuchi, S.; Ohtsu, A.; Doi, T.; Kojima, T.; Minashi, K.; Mera, K.; Yano, T.; Tahara, M.; Muto, M.; Nihei, K. A retrospective study of definitive chemoradiotherapy for elderly patients with esophageal cancer. Am. J. Clin. Oncol., 2007, 30(6), 607-611.
[http://dx.doi.org/10.1097/COC.0b013e3180ca7c84] [PMID: 18091055]
[11]
Tougeron, D.; Di Fiore, F.; Thureau, S.; Berbera, N.; Iwanicki-Caron, I.; Hamidou, H.; Paillot, B.; Michel, P. Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer. Br. J. Cancer, 2008, 99(10), 1586-1592.
[http://dx.doi.org/10.1038/sj.bjc.6604749] [PMID: 19002180]
[12]
Hino, K.; Kajiwara, T.; Nishina, T.; Inoue, T.; Yoshimatsu, M.; Sakaguchi, C.; Nakasya, A.; Nishide, N.; Asagi, A.; Hasebe, A.; Terao, T.; Hori, S.; Nadano, S.; Hamamoto, Y.; Kataoka, M.; Tanimizu, M. Tolerability of definitive chemoradiotherapy in elderly patients with esophageal cancer. Gan To Kagaku Ryoho, 2020, 47(11), 1577-1581.
[PMID: 33268731]
[13]
Crombet Ramos, T.; Mestre Fernández, B.; Mazorra Herrera, Z.; Iznaga Escobar, N.E. Nimotuzumab for patients with inoperable cancer of the head and neck. Front. Oncol., 2020, 10, 817.
[http://dx.doi.org/10.3389/fonc.2020.00817] [PMID: 32537431]
[14]
Ang, M.K.; Montoya, J.E.; Tharavichitkul, E.; Lim, C.; Tan, T.; Wang, L.Y.; Wee, J.; Soong, Y.L.; Fong, K.W.; Ng, Q.S.; Tan, D.S.W.; Toh, C.K.; Tan, E.H.; Lim, W.T. Phase II study of nimotuzumab (THERACIM‐HR3) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma. Head Neck, 2021, 43(5), 1641-1651.
[http://dx.doi.org/10.1002/hed.26635] [PMID: 33547683]
[15]
Patil, V.M.; Kumar Singh, G.; Noronha, V.; Joshi, A.; Menon, N.; Ghosh Lashkar, S.; Mathrudev, V.; Nawale Satam, K.; Abdulazeez Mukadam, S.; Prabhash, K. Lymphopenia during chemoradiation—foe or friend. Ecancer med. Sci., 2020, 14, 1109.
[http://dx.doi.org/10.3332/ecancer.2020.1109] [PMID: 33144877]
[16]
Sunpaweravong, P.; Sunpaweravong, S.; Puttawibul, P.; Mitarnun, W.; Zeng, C.; Barón, A.E.; Franklin, W.; Said, S.; Varella-Garcia, M. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J. Cancer Res. Clin. Oncol., 2005, 131(2), 111-119.
[http://dx.doi.org/10.1007/s00432-004-0610-7] [PMID: 15672286]
[17]
Hanawa, M.; Suzuki, S.; Dobashi, Y.; Yamane, T.; Kono, K.; Enomoto, N.; Ooi, A. EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int. J. Cancer, 2006, 118(5), 1173-1180.
[http://dx.doi.org/10.1002/ijc.21454] [PMID: 16161046]
[18]
Ramos-Suzarte, M.; Lorenzo-Luaces, P.; Lazo, N.G.; Perez, M.L.; Soriano, J.L.; Gonzalez, C.E.V.; Hernadez, I.M.; Albuerne, Y.Á.; Moreno, B.P.; Alvarez, E.S.; Callejo, I.P.; Alert, J.; Martell, J.A.; Gonzalez, Y.S.; Gonzalez, Y.S.; Astudillo de la Vega, H.; Ruiz-Garcia, E.B.; Ramos, T.C. Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol. Ther., 2012, 13(8), 600-605.
[http://dx.doi.org/10.4161/cbt.19849] [PMID: 22555809]
[19]
de Castro, J. A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced esophageal carcinoma: Nice trial. Eur. J. Cancer, 2018, 88, 21-30.
[20]
al-Sarraf, M.; Martz, K.; Herskovic, A.; Leichman, L.; Brindle, J.S.; Vaitkevicius, V.K.; Cooper, J.; Byhardt, R.; Davis, L.; Emami, B. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: An intergroup study. J. Clin. Oncol., 1997, 15(1), 277-284.
[http://dx.doi.org/10.1200/JCO.1997.15.1.277] [PMID: 8996153]
[21]
Liang, J.; e, M.; Wu, G.; Zhao, L.; Li, X.; Xiu, X.; Li, N.; Chen, B.; Hui, Z.; Lv, J.; Fang, H.; Tang, Y.; Bi, N.; Wang, W.; Zhai, Y.; Li, T.; Chen, D.; Zou, S.; Lu, N.; Perez-Rodríguez, R.; Zheng, J.; Wang, L. Nimotuzumab combined with radiotherapy for esophageal cancer: Preliminary study of a Phase II clinical trial. OncoTargets Ther., 2013, 6, 1589-1596.
[http://dx.doi.org/10.2147/OTT.S50945] [PMID: 24235844]
[22]
Ji, Y.; Du, X.; Zhu, W.; Yang, Y.; Ma, J.; Zhang, L.; Li, J.; Tao, H.; Xia, J.; Yang, H.; Huang, J.; Bao, Y.; Du, D.; Liu, D.; Wang, X.; Li, C.; Yang, X.; Zeng, M.; Liu, Z.; Zheng, W.; Pu, J.; Chen, J.; Hu, W.; Li, P.; Wang, J.; Xu, Y.; Zheng, X.; Chen, J.; Wang, W.; Tao, G.; Cai, J.; Zhao, J.; Zhu, J.; Jiang, M.; Yan, Y.; Xu, G.; Bu, S.; Song, B.; Xie, K.; Huang, S.; Zheng, Y.; Sheng, L.; Lai, X.; Chen, Y.; Cheng, L.; Hu, X.; Ji, W.; Fang, M.; Kong, Y.; Yu, X.; Li, H.; Li, R.; Shi, L.; Shen, W.; Zhu, C.; Lv, J.; Huang, R.; He, H.; Chen, M. Efficacy of concurrent chemoradiotherapy with S-1 vs. radiotherapy alone for older patients with esophageal cancer. JAMA Oncol., 2021, 7(10), 1459-1466.
[http://dx.doi.org/10.1001/jamaoncol.2021.2705] [PMID: 34351356]
[23]
Yang, X.; Zhai, Y.; Bi, N.; Zhang, T.; Deng, L.; Wang, W.; Wang, X.; Chen, D.; Zhou, Z.; Wang, L.; Liang, J. Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients: A phase II clinical trial. Chin. J. Cancer Res., 2021, 33(1), 53-60.
[http://dx.doi.org/10.21147/j.issn.1000-9604.2021.01.06] [PMID: 33707928]
[24]
Münch, S.; Pigorsch, S.U.; Devečka, M.; Dapper, H.; Weichert, W.; Friess, H.; Braren, R.; Combs, S.E.; Habermehl, D. Comparison of definite chemoradiation therapy with carboplatin/paclitaxel or cisplatin/5-fluoruracil in patients with squamous cell carcinoma of the esophagus. Radiat. Oncol., 2018, 13(1), 139.
[http://dx.doi.org/10.1186/s13014-018-1085-z] [PMID: 30068371]
[25]
Guo, J.H.; Chen, M.Q.; Chen, C.; Lu, H.J.; Xu, B.H. Efficacy and toxicity of nimotuzumab combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma. Mol. Clin. Oncol., 2015, 3(5), 1135-1138.
[http://dx.doi.org/10.3892/mco.2015.606] [PMID: 26623065]
[26]
Qin, S.; Li, J.; Wang, L.; Xu, J.; Cheng, Y.; Bai, Y.; Li, W.; Xu, N.; Lin, L.; Wu, Q.; Li, Y.; Yang, J.; Pan, H.; Ouyang, X.; Qiu, W.; Wu, K.; Xiong, J.; Dai, G.; Liang, H.; Hu, C.; Zhang, J.; Tao, M.; Yao, Q.; Wang, J.; Chen, J.; Eggleton, S.P.; Liu, T. Efficacy and tolerability of first-line cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) versus FOLFOX-4 in patients with RAS wild-type metastatic colorectal cancer: The open-label, randomized, phase III tailor trial. J. Clin. Oncol., 2018, 36(30), 3031-3039.
[http://dx.doi.org/10.1200/JCO.2018.78.3183] [PMID: 30199311]
[27]
James, A. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N. Engl. J. Med., 2006, 354, 567-578.
[28]
Suntharalingam, M.; Winter, K.; Ilson, D.; Dicker, A.P.; Kachnic, L.; Konski, A.; Chakravarthy, A.B.; Anker, C.J.; Thakrar, H.; Horiba, N.; Dubey, A.; Greenberger, J.S.; Raben, A.; Giguere, J.; Roof, K.; Videtic, G.; Pollock, J.; Safran, H.; Crane, C.H. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer. JAMA Oncol., 2017, 3(11), 1520-1528.
[http://dx.doi.org/10.1001/jamaoncol.2017.1598] [PMID: 28687830]
[29]
Thomas, C. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): A multicentre, phase 2/3 randomised trial. Lancet Oncol., 2013, 14, 627-637.
[30]
Jing, W.; Yan, W.; Liu, Y.; Li, J.; Yu, J.; Zhu, H. Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma. Cancer Biol. Ther., 2019, 20(8), 1121-1126.
[http://dx.doi.org/10.1080/15384047.2019.1598760] [PMID: 30983494]
[31]
Xu, Y.; Zheng, Y.; Sun, X.; Yu, X.; Gu, J.; Wu, W.; Zhang, G.; Hu, J.; Sun, W.; Mao, W. Concurrent radiotherapy with gefitinib in elderly patients with esophageal squamous cell carcinoma: Preliminary results of a phase II study. Oncotarget, 2015, 6(35), 38429-38439.
[http://dx.doi.org/10.18632/oncotarget.5193] [PMID: 26392415]
[32]
Iyer, R.; Chhatrala, R.; Shefter, T.; Yang, G.; Malhotra, U.; Tan, W.; LeVea, C.; Robins, M.; Khushalani, N. Erlotinib and radiation therapy for elderly patients with esophageal cancer - clinical and correlative results from a prospective multicenter phase 2 trial. Oncology, 2013, 85(1), 53-58.
[http://dx.doi.org/10.1159/000351617] [PMID: 23860007]
[33]
Luo, H.; Jiang, W.; Ma, L.; Chen, P.; Fang, M.; Ding, L.; Hua, Y.; Du, D.; Jing, Z.; Xie, R.; Song, Y.; Wang, J.; Zhou, R.; Tian, Z.; Wu, S. Icotinib with concurrent radiotherapy vs. radiotherapy alone in older adults with unresectable esophageal squamous cell carcinoma. JAMA Netw. Open, 2020, 3(10), e2019440.
[http://dx.doi.org/10.1001/jamanetworkopen.2020.19440] [PMID: 33026449]
[34]
Jia, J.; Cui, Y.; Lu, M.; Wang, X.; Li, J.; Li, J.; Li, Y.; Zhang, X.; Gao, J.; Zhou, J.; Lu, Z.; Gong, J.; Yu, J.; Sun, Z.; Liu, C.; Shen, L.; Zhang, X. The relation of EGFR expression by immunohistochemical staining and clinical response of combination treatment of nimotuzumab and chemotherapy in esophageal squamous cell carcinoma. Clin. Transl. Oncol., 2016, 18(6), 592-598.
[http://dx.doi.org/10.1007/s12094-015-1406-8] [PMID: 26459251]

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