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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis

Authors: Hao Peng, Ling-Long Tang, Xu Liu, Lei Chen, Wen-Fei Li, Yan-Ping Mao, Yuan Zhang, Li-Zhi Liu, Li Tian, Ying Guo, Ying Sun, Jun Ma

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Little is known about the prognostic difference of anti-EGFR therapy, cetuximab (CTX) or nimotuzumab (NTZ), concurrently with induction chemotherapy (IC, investigational arm) or RT (control arm) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We conducted this retrospective study to address this.

Methods

We identified 296 patients with newly diagnosed LA-NPC at Sun Yat-Sen University Cancer Center between January 2012 and May 2015. Patients were treated by IC with CCRT or RT and CTX/NTZ was delivered during IC or radiotherapy. Survival outcomes and toxicities between different arms were compared.

Results

In total, there were 149 patients in the investigational arm and 147 in control arm. The 3-year disease-free survival, overall survival, distant metastasis-free survival and locoregional relapse-free survival rates for investigational arm vs. control arm were 84.3% vs. 74.3% (P = 0.027), 94.0% vs. 92.1% (P = 0.673), 88.0% vs. 81.8% (P = 0.147) and 93.3% vs. 88.0% (P = 0.093). Multivariate analysis revealed patients in the control arm achieved significantly worse disease-free survival (HR, 1.497; 95% CI, 1.016–2.206; P = 0.026) compared with those in the investigational arm; however, no significant difference was identified for other endpoints. Patients in the investigational arm experienced more grade 3–4 skin reaction (15.4% vs. 2.0%, P <  0.001) and mucositis (10.1% vs. 3.4%, P = 0.022) during induction phase, but less skin reaction (5.4% vs. 25.9%, P <  0.001) and mucositis (24.8% vs. 36.7%, P = 0.026) during RT.

Conclusions

Our findings suggested that CTX/NTZ concurrently with IC may be a more effective and promising strategy for patients with LA-NPC receiving intensity-modulated radiotherapy.
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Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
go back to reference Yi JL, Gao L, Huang XD, et al. Nasopharyngeal carcinoma treated by radical radiotherapy alone: ten-year experience of a single institution. Int J Radiat Oncol Biol Phys. 2006;65:161–8.CrossRefPubMed Yi JL, Gao L, Huang XD, et al. Nasopharyngeal carcinoma treated by radical radiotherapy alone: ten-year experience of a single institution. Int J Radiat Oncol Biol Phys. 2006;65:161–8.CrossRefPubMed
3.
go back to reference Mao YP, Xie FY, Liu LZ, et al. Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009;73:1326–34.CrossRefPubMed Mao YP, Xie FY, Liu LZ, et al. Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009;73:1326–34.CrossRefPubMed
4.
go back to reference Lai SZ, Li WF, Chen L, et al. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80:661–8.CrossRefPubMed Lai SZ, Li WF, Chen L, et al. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80:661–8.CrossRefPubMed
6.
go back to reference Ciardiello F, Tortora GA. Novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 2001;7:2958–70.PubMed Ciardiello F, Tortora GA. Novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 2001;7:2958–70.PubMed
7.
go back to reference Mendelsohn J. Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol. 2002;20(18 Suppl):1S–13S.PubMed Mendelsohn J. Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol. 2002;20(18 Suppl):1S–13S.PubMed
8.
go back to reference Ma BB, Poon TC, To KF, 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;25:864–72.CrossRefPubMed Ma BB, Poon TC, To KF, 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;25:864–72.CrossRefPubMed
9.
go back to reference He X, Xu J, Guo W, et al. Cetuximab in combination with chemoradiation after induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma: preliminary results. Future Oncol. 2013;9:1459–67.CrossRefPubMed He X, Xu J, Guo W, et al. Cetuximab in combination with chemoradiation after induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma: preliminary results. Future Oncol. 2013;9:1459–67.CrossRefPubMed
10.
go back to reference Li Y, Chen QY, Tang LQ, et al. Concurrent chemoradiotherapy with or without cetuximab for stage II to IVb nasopharyngeal carcinoma: a case-control study. BMC Cancer. 2017;17:567.CrossRefPubMedPubMedCentral Li Y, Chen QY, Tang LQ, et al. Concurrent chemoradiotherapy with or without cetuximab for stage II to IVb nasopharyngeal carcinoma: a case-control study. BMC Cancer. 2017;17:567.CrossRefPubMedPubMedCentral
11.
go back to reference Xia WX, Liang H, Lv X, et al. Combining cetuximab with chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: a propensity score analysis. Oral Oncol. 2017;67:167–74.CrossRefPubMed Xia WX, Liang H, Lv X, et al. Combining cetuximab with chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: a propensity score analysis. Oral Oncol. 2017;67:167–74.CrossRefPubMed
12.
go back to reference Xu 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;51:875–9.CrossRefPubMed Xu 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;51:875–9.CrossRefPubMed
13.
go back to reference You R, Hua YJ, Liu YP, 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;7:2314–24.CrossRefPubMedPubMedCentral You R, Hua YJ, Liu YP, 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;7:2314–24.CrossRefPubMedPubMedCentral
14.
go back to reference You R, Sun R, Hua YJ, et al. Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma. Int J Cancer. 2017;141:1265–76.CrossRefPubMed You R, Sun R, Hua YJ, et al. Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma. Int J Cancer. 2017;141:1265–76.CrossRefPubMed
15.
go back to reference Huang JF, Zhang FZ, Zou QZ, et al. Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial. Oncotarget. 2017;8:2457–65.PubMed Huang JF, Zhang FZ, Zou QZ, et al. Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial. Oncotarget. 2017;8:2457–65.PubMed
16.
go back to reference Cao SM, Yang Q, Guo L, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase III multicentre randomised controlled trial. Eur J Cancer. 2017;75:14–23.CrossRefPubMed Cao SM, Yang Q, Guo L, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase III multicentre randomised controlled trial. Eur J Cancer. 2017;75:14–23.CrossRefPubMed
17.
go back to reference Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242–9.CrossRefPubMed Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242–9.CrossRefPubMed
18.
go back to reference Peng H, Chen L, Zhang J, et al. Induction chemotherapy improved long-term outcomes of patients with Locoregionally advanced nasopharyngeal carcinoma: a propensity matched analysis of 5-year survival outcomes in the era of intensity-modulated radiotherapy. J Cancer. 2017;8:371–7.CrossRefPubMedPubMedCentral Peng H, Chen L, Zhang J, et al. Induction chemotherapy improved long-term outcomes of patients with Locoregionally advanced nasopharyngeal carcinoma: a propensity matched analysis of 5-year survival outcomes in the era of intensity-modulated radiotherapy. J Cancer. 2017;8:371–7.CrossRefPubMedPubMedCentral
19.
go back to reference Sun Y, Li WF, Chen NY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17:1509–20.CrossRefPubMed Sun Y, Li WF, Chen NY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17:1509–20.CrossRefPubMed
20.
go back to reference Edge SB, Compton CC. The American joint committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed Edge SB, Compton CC. The American joint committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed
21.
go back to reference Peng H, Chen L, Li WF, et al. Optimize the cycle of neoadjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a propensity score matching analysis. Oral Oncol. 2016;62:78–84.CrossRefPubMed Peng H, Chen L, Li WF, et al. Optimize the cycle of neoadjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a propensity score matching analysis. Oral Oncol. 2016;62:78–84.CrossRefPubMed
22.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed
23.
go back to reference Sun X, Su S, Chen C, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2014;110:398–403.CrossRefPubMed Sun X, Su S, Chen C, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2014;110:398–403.CrossRefPubMed
24.
go back to reference Lin JC, Liang WM, Jan JS, Jiang RS, Lin AC. Another way to estimate outcome of advanced nasopharyngeal carcinoma--is concurrent chemoradiotherapy adequate? Int J Radiat Oncol Biol Phys. 2004;60:156–64.CrossRefPubMed Lin JC, Liang WM, Jan JS, Jiang RS, Lin AC. Another way to estimate outcome of advanced nasopharyngeal carcinoma--is concurrent chemoradiotherapy adequate? Int J Radiat Oncol Biol Phys. 2004;60:156–64.CrossRefPubMed
25.
go back to reference Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005;23:3568–76.CrossRefPubMed Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005;23:3568–76.CrossRefPubMed
26.
go back to reference Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.CrossRefPubMed Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.CrossRefPubMed
27.
go back to reference Pfister DG, Su YB, Kraus DH, et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. J Clin Oncol. 2006;24:1072–8.CrossRefPubMed Pfister DG, Su YB, Kraus DH, et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. J Clin Oncol. 2006;24:1072–8.CrossRefPubMed
28.
go back to reference Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.CrossRefPubMed Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.CrossRefPubMed
29.
go back to reference Fang FM, Chiu HC, Kuo WR, et al. Health-related quality of life for nasopharyngeal carcinoma patients with cancer-free survival after treatment. Int J Radiat Oncol Biol Phys. 2002;53:959–68.CrossRefPubMed Fang FM, Chiu HC, Kuo WR, et al. Health-related quality of life for nasopharyngeal carcinoma patients with cancer-free survival after treatment. Int J Radiat Oncol Biol Phys. 2002;53:959–68.CrossRefPubMed
30.
go back to reference Fang FM, Tsai WL, Chien CY, et al. Pretreatment quality of life as a predictor of distant metastasis and survival for patients with nasopharyngeal carcinoma. J Clin Oncol. 2010;28:4384–9.CrossRefPubMed Fang FM, Tsai WL, Chien CY, et al. Pretreatment quality of life as a predictor of distant metastasis and survival for patients with nasopharyngeal carcinoma. J Clin Oncol. 2010;28:4384–9.CrossRefPubMed
31.
go back to reference Kwong DL, Sham JS, Chua DT, Choy DT, Au GK, Wu PM. The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1997;39:703–10.CrossRefPubMed Kwong DL, Sham JS, Chua DT, Choy DT, Au GK, Wu PM. The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1997;39:703–10.CrossRefPubMed
32.
go back to reference Li PJ, Jin T, Luo DH, et al. Effect of prolonged radiotherapy treatment time on survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma. PLoS One. 2015;10:e0141332.CrossRefPubMedPubMedCentral Li PJ, Jin T, Luo DH, et al. Effect of prolonged radiotherapy treatment time on survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma. PLoS One. 2015;10:e0141332.CrossRefPubMedPubMedCentral
Metadata
Title
Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis
Authors
Hao Peng
Ling-Long Tang
Xu Liu
Lei Chen
Wen-Fei Li
Yan-Ping Mao
Yuan Zhang
Li-Zhi Liu
Li Tian
Ying Guo
Ying Sun
Jun Ma
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4268-y

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