Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-10T15:02:49.940Z Has data issue: false hasContentIssue false
  • English
  • Français

Cetuximab in the management of nasopharyngeal carcinoma – a narrative review

Published online by Cambridge University Press:  11 September 2019

M S Iqbal ,
D Wilkinson ,
A Tin ,
P Bossi ,
L Gradwell-Nelson ,
J Kovarik ,
J O'Hara  and
C Kelly
M S Iqbal*
Affiliation:
Department of Clinical Oncology, Northern Centre for Cancer Care, Newcastle upon Tyne NHS Hospitals Foundation Trust, UK
D Wilkinson
Affiliation:
Department of Clinical Oncology, James Cook University Hospital, Middlesbrough, UK
A Tin
Affiliation:
Department of Clinical Oncology, James Cook University Hospital, Middlesbrough, UK
P Bossi
Affiliation:
Department of Oncology, Istituto Nazionale dei Tumori, Milan, Italy
L Gradwell-Nelson
Affiliation:
Department of Otolaryngology, Newcastle upon Tyne NHS Hospitals Foundation Trust, UK
J Kovarik
Affiliation:
Department of Clinical Oncology, Northern Centre for Cancer Care, Newcastle upon Tyne NHS Hospitals Foundation Trust, UK
J O'Hara
Affiliation:
Department of Otolaryngology, Newcastle upon Tyne NHS Hospitals Foundation Trust, UK
C Kelly
Affiliation:
Department of Clinical Oncology, Northern Centre for Cancer Care, Newcastle upon Tyne NHS Hospitals Foundation Trust, UK
*
Author for correspondence: Dr Muhammad Shahid Iqbal, Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK E-mail: shahid.iqbal@nhs.net
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.

Method

A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.

Results

Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.

Conclusion

There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.

Keywords

Nasopharyngeal CarcinomaCetuximabReview
Type
Review Articles
Information
The Journal of Laryngology & Otology , Volume 133 , Issue 10 , October 2019 , pp. 843 - 855
Copyright
Copyright © JLO (1984) Limited, 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Dr M S Iqbal takes responsibility for the integrity of the content of the paper

References

1Lee, AW, Lin, JC, Ng, WT. Current management of nasopharyngeal cancer. Semin Radiat Oncol 2012;22:233–44Google Scholar
2You, R, Cao, YS, Huang, PY, Chen, L, Yang, Q, Liu, YP et al. The changing therapeutic role of chemo-radiotherapy for loco-regionally advanced nasopharyngeal carcinoma from two/three-dimensional radiotherapy to intensity-modulated radiotherapy: a network meta-analysis. Theranostics 2017;7:4825–35Google Scholar
3Al-Sarraf, M, LeBlanc, M, Giri, PG, Fu, KK, Cooper, J, Vuong, T et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998;16:1310–17Google Scholar
4Putti, TC, To, KF, Hsu, HC, Chan, AT, Lai, GM, Tse, G et al. Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia-Pacific region. Histopathology 2002;41:144–51Google Scholar
5Ma, BB, Poon, TC, To, KF, Zee, B, Mo, FK, Chan, CM et al. Prognostic significance of tumor angiogenesis, Ki 67, p53 oncoprotein, epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma--a prospective study. Head Neck 2003;25:864–72Google Scholar
6Chua, DT, Nicholls, JM, Sham, JS, Au, GK. Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys 2004;59:11–20Google Scholar
7Bonner, JA, Harari, PM, Giralt, J, Cohen, RB, Jones, CU, Sur, RK et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11:21–8Google Scholar
8Vermorken, JB, Mesia, R, Rivera, F, Remenar, E, Kawecki, A, Rottey, S et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116–27Google Scholar
9Feng, HX, Guo, SP, Li, GR, Zhong, WH, Chen, L, Huang, LR et al. Toxicity of concurrent chemoradiotherapy with cetuximab for locoregionally advanced nasopharyngeal carcinoma. Med Oncol 2014;31:170Google Scholar
10Zhang, X, Du, L, Zhao, F, Wang, Q, Yang, S, Ma, L. A phase II clinical trial of concurrent helical tomotherapy plus cetuximab followed by adjuvant chemotherapy with cisplatin and docetaxel for locally advanced nasopharyngeal carcinoma. Int J Biol Sci 2016;12:446–53Google Scholar
11Chen, C, Zhao, C, Gao, L, Lang, J, Pan, J, Hu, C et al. Long-term result of a multicenter clinical study of cetuximab combined with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). J Clin Oncol 2015;33(15 suppl):e17020Google Scholar
12Wu, LR, Zhu, HF, Xu, J, Jiang, XS, Yin, L, Jiang, N et al. Effectiveness of cetuximab in combination with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a 1:2 propensity score-matched analysis. J Cancer 2018;9:1642–51Google Scholar
13Li, Y, Chen, QY, Tang, LQ, Liu, LT, Guo, SS, Guo, L et al. Concurrent chemoradiotherapy with or without cetuximab for stage II to IVb nasopharyngeal carcinoma: a case-control study. BMC Cancer 2017;17:567Google Scholar
14He, X, Xu, J, Guo, W, Jiang, X, Wang, X, Zong, D. Cetuximab in combination with chemoradiation after induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma: preliminary results. Future Oncol 2013;9:1459–67Google Scholar
15Ma, BB, Kam, MK, Leung, SF, Hui, EP, King, AD, Chan, SL et al. A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Ann Oncol 2012;23:1287–92Google Scholar
16Xia, WX, Liang, H, Lv, X, Wang, L, Qian, CN, Ye, YF et al. Combining cetuximab with chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: a propensity score analysis. Oral Oncol 2017;67:167–74Google Scholar
17You, R, Hua, YJ, Liu, YP, Yang, Q, Zhang, YN, Li, JB et al. Concurrent chemoradiotherapy with or without anti-EGFR-targeted treatment for stage II-IVb nasopharyngeal carcinoma: retrospective analysis with a large cohort and long follow-up. Theranostics 2017;7:2314–24Google Scholar
18Zhu, G, Liu, Y, Guan, X, Hu, C, Li, F. Induction chemotherapy followed by concomitant chemoradiation versus cetuximab with radiation in locally-advanced nasopharyngeal carcinoma: initial results of a randomized phase 2 study. Int J Radiat Oncol Biol Phys 2013;87:S193Google Scholar
19Wu, X, Huang, J, Liu, L, Li, H, Li, P, Zhang, J et al. Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma: a retrospective matched case-control study. Medicine (Baltimore) 2016;95:e4926Google Scholar
20Xu, T, Liu, Y, Dou, S, Li, F, Guan, X, Zhu, G. Weekly cetuximab concurrent with IMRT aggravated radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma: results of a randomized phase II study. Oral Oncol 2015;51:875–9Google Scholar
21Niu, X, Hu, C, Kong, L. Experience with combination of cetuximab plus intensity-modulated radiotherapy with or without chemotherapy for locoregionally advanced nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2013;139:1063–71Google Scholar
22Lin, PJ, Wang, WY, Liu, YC, Lin, JC. Treatment outcome of induction bio-chemotherapy followed by IMRT in advanced NPC patients. Radiother Oncol 2016;119(suppl 1):S508Google Scholar
23Peng, H, Tang, LL, Liu, X, Chen, L, Li, WF, Mao, YP et al. Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis. BMC Cancer 2018;18:323Google Scholar
24Ng, WT, Ngan, RKC, Kwong, DLW, Tung, SY, Yuen, KT, Kam, MKM et al. Prospective, multicenter, phase 2 trial of induction chemotherapy followed by bio-chemoradiotherapy for locally advanced recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2018;100:630–8Google Scholar
25Chan, AT, Hsu, MM, Goh, BC, Hui, EP, Liu, TW, Millward, MJ et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol 2005;23:3568–76Google Scholar
26Kerboua, E, Tahrat, A, Bouzid, K. A open label phase II trial of cetuximab plus cisplatin in patients with recurrent or metastatic undifferentiated carcinoma of nasopharyngeal type: results after three years. J Clin Oncol 2015;33:e17021Google Scholar
27Lin, T, Zhang, M, Huang, H, Li, X, Huang, Y, Chen, C et al. Prospective study of cetuximab with cisplatin plus docetaxel followed by concurrent radiotherapy plus cetuximab and cisplatin in patients with chemotherapy-naive metastatic nasopharyngeal carcinoma. Ann Oncol 2016;27(suppl 6):974Google Scholar
28Xu, T, Ou, X, Shen, C, Hu, C. Cetuximab in combination with chemoradiotherapy in the treatment of recurrent and/or metastatic nasopharyngeal carcinoma. Anticancer Drugs 2016;27:66–70Google Scholar
29Blanchard, P, Lee, A, Marguet, S, Leclercq, J, Ng, WT, Ma, J et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol 2015;16:645–55Google Scholar
30Ribassin-Majed, L, Marguet, S, Lee, AWM, Ng, WT, Ma, J, Chan, ATC et al. What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis. J Clin Oncol 2017;35:498–505Google Scholar
31Specenier, PM, Remenar, E, Buter, J, Schrijvers, DL, Bergamini, C, Licitra, LF et al. TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial. Ann Oncol 2017;28:2219–24Google Scholar
32Licitra, L, Bossi, P, Locati, LD, Bergamini, C. Is restoring platinum sensitivity the best goal for cetuximab in recurrent/metastatic nasopharyngeal cancer? J Clin Oncol 2005;23:7757–8Google Scholar