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Current Cancer Drug Targets

Editor-in-Chief

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

Clinical Trial

Efficacy and Safety of Concurrent Chemoradiotherapy Combined with Nimotuzumab in Elderly Patients with Esophageal Squamous Cell Carcinoma: A Prospective Real-world Pragmatic Study

Author(s): Nuo Yu, Guowei Cheng, Jiao Li, Jun Liang, Tao Zhang, Lei Deng, Wenyang Liu, Jianyang Wang, Yirui Zhai, Wenqing Wang, Zefen Xiao, Zongmei Zhou, Dongfu Chen, Qinfu Feng, Nan Bi and Xin Wang*

Volume 23, Issue 8, 2023

Published on: 27 April, 2023

Page: [653 - 662] Pages: 10

DOI: 10.2174/1568009623666230315145937

Price: $65

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Abstract

Background: Concurrent or definitive chemoradiotherapy is the standard treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Elderly patients could not tolerate the standard concurrent chemotherapy and were treated with radiotherapy because of weak physical status and multiple comorbidities.

Objective: The efficacy and safety profile of concurrent (chemo) radiotherapy combined with nimotuzumab in elderly patients with ESCC were investigated.

Methods: Eligible elderly (≥70 years) patients with locally advanced ESCC were enrolled in this prospective, real-world pragmatic study and received concurrent chemoradiotherapy or radiotherapy combined with nimotuzumab. The primary endpoint was overall survival (OS). Secondary endpoints were objective response rate, disease control rate, progression-free survival (PFS), and adverse drug reactions.

Results: Fifty-three elderly patients were enrolled. Thirty-two (60.4%) were treated with radiotherapy combined with nimotuzumab (RT+N), and 21 (39.6%) with concurrent chemoradiotherapy combined with nimotuzumab (CRT+N). The median age was 75.8 years. Fourteen (56.0%) patients achieved a partial response, and 11 (44.0%) patients achieved stable disease at 3 months. The median follow-up duration was 24.4 (95%CI, 21.6-26.7) months. Median OS (mOS) was 27.0 (95%CI, 14.8-48.4) months. Median PFS (mPFS) was 22.6 (95%CI, 12.4-not reached) months. Higher mPFS (not reached vs. 12.0 months; p=0.022) and mOS (48.4 vs. 15.3 months; p=0.009) were observed in the CRT+N group compared with the RT+N group. Most adverse reactions were grade 1-2 (46, 86.8%).

Conclusions: Concurrent chemoradiotherapy or radiotherapy combined with nimotuzumab was safe and well-tolerated in elderly patients with locally advanced ESCC. ESCC patients treated with CRT+N could live longer.

Keywords: ESCC, nimotuzumab, elderly patients, chemoradiotherapy, overall survival, progression-free survival.

Graphical Abstract
[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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