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      Efficacy and safety of nimotuzumab with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma

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          Abstract

          We assessed the efficacy and safety of nimotuzumab plus neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for Chinese patients with locoregionally advanced nasopharyngeal carcinoma. Clinical data from 210 nonmetastatic nasopharyngeal carcinoma patients diagnosed between May 2008 and April 2014 were retrospectively reviewed. All patients were initially treated with nimotuzumab plus neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Ninety-five patients received cisplatin-based adjuvant chemotherapy. The median follow-up duration was 48 months. Locoregional relapse and distant metastases occurred in 16 patients (16/210, 7.6%) and 18 patients (18/210, 8.6%), respectively. The 5-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival rates were 95.6%, 94.4%, 91.7%, 84.0%, and 88.7%, respectively. Univariate analysis revealed that concurrent chemotherapy regimens and clinical stage correlated with overall survival, and that adjuvant chemotherapy, N stage, clinical stage, and tumor response at the end of treatment were correlated with progression-free survival. In the multivariate analysis, concurrent chemotherapy regimens, clinical stage, and tumor response were important prognosticators. Grade 3/4 leukocytopenia was experienced by 24 patients (11.4%), and 6 patients (2.9%) developed mild liver damage during the period of neoadjuvant chemotherapy. Grade 3/4 acute mucositis was experienced by 13 patients (6.2%), and 12 patients (5.7%) experienced grade 3/4 leukocytopenia during the concurrent chemotherapy. The efficacy of nimotuzumab plus neoadjuvant chemotherapy followed by concurrent chemotherapy in locoregionally advanced nasopharyngeal carcinoma patients was encouraging and the toxicities were tolerable.

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          Most cited references29

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          Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

          The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.
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            How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?

            To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC). A retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients. Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups. A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients.

              To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                26 September 2017
                21 April 2017
                : 8
                : 43
                : 75544-75556
                Affiliations
                1 Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang Hangzhou, People’s Republic of China
                2 Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Hangzhou, People’s Republic of China
                3 Department of Breast Tumor Surgery, Zhejiang Cancer Hospital, Zhejiang Hangzhou, People’s Republic of China
                4 Department of Physics, Zhejiang Cancer Hospital, Zhejiang Hangzhou, People’s Republic of China
                5 Department of Pathology, Zhejiang Cancer Hospital, Zhejiang Hangzhou, People’s Republic of China
                6 Department of Ultrasonography, Zhejiang Cancer Hospital, Zhejiang Hangzhou, People’s Republic of, China
                7 Department of Nuclear Medicine, Zhejiang Cancer Hospital, Zhejiang Hangzhou, People’s Republic of China
                8 Department of Radiology, Japanese Red Cross Fukui Hospital, Fukui, Japan
                Author notes
                Correspondence to : Fangzheng Wang, wangfz76@ 123456126.com
                [*]

                These authors have contributed equally to this work

                Article
                17357
                10.18632/oncotarget.17357
                5650444
                de0b98f0-d86b-4c3b-b67a-537ee9c36ccd
                Copyright: © 2017 Wang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 January 2017
                : 11 April 2017
                Categories
                Clinical Research Paper

                Oncology & Radiotherapy
                nasopharyngeal carcinoma,nimotuzumab,neoadjuvant chemotherapy,concurrent chemotherapy,intensity-modulated radiotherapy

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