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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 6  |  Page : 205-208

A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma


1 Department of Pharmacy, Jinhua Central Hospital, Zhejiang Province 321000, China
2 Department of Otorhinolaryngology, Lishui People’s Hospital, Zhejiang Province 323000, China
3 Department of Lishui People’s Hospital, Zhejiang Province 323000, China

Date of Web Publication26-Oct-2015

Correspondence Address:
Lixian Liu
Department of Pharmacy, Lishui People’s Hospital, Zhejiang Province 323000
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.168186

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 > Abstract 

Objective: We perform this meta-analysis was to evaluate the efficacy of neoadjuvant chemotherapy followed by radiation in the treatment of locally advanced nasopharyngeal carcinoma.
Materials and Methods: We searched the database of Medline and Wanfang to screen and included the prospective, randomized controlled trials of neoadjuvant chemotherapy plus radiation versus radiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. The pooled 5-year overall survival, 5 years disease free survival, recurrence rate, and metastasis rate were calculated by Stata version 11.0 statistical software.
Results: Five prospective clinical studies were included in this meta-analysis. The total number of cases included in this study was 1277. The pooled 5 years overall survival and 5 years disease free survival were not statistical different between the neoadjuvant chemotherapy plus radiation group and radiotherapy group, respectively (P > 0.05). But the recurrence rate (odds ratio [OR] = 0.65, P < 0.05) and metastasis rate (OR = 0.61, P < 0.05) were significantly lower in the neoadjuvant chemotherapy plus radiation group compared to radiotherapy group.
Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma.

Keywords: Meta-analysis, metastasis, nasopharyngeal carcinoma, neoadjuvant chemotherapy, prognosis, radiation, recurrence


How to cite this article:
He X, Xu K, Guo J, Zhu Y, Liang X, Liu L. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma. J Can Res Ther 2015;11, Suppl S2:205-8

How to cite this URL:
He X, Xu K, Guo J, Zhu Y, Liang X, Liu L. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma. J Can Res Ther [serial online] 2015 [cited 2020 Sep 29];11:205-8. Available from: http://www.cancerjournal.net/text.asp?2015/11/6/205/168186


 > Introduction Top


Nasopharyngeal carcinoma is one of the most common diagnosed malignant squamous cell head and neck carcinoma.[1] In China, nasopharyngeal carcinoma is mainly occurred in the south part such as Guangdong, Guangxi, and Fujian Province.[2],[3] Early stages patient (I and II) take part in about 30% with relative good prognosis treated with radical radiotherapy. However, the prognosis of locally advanced or advanced nasopharyngeal carcinoma (III and IV) was relatively poor.[1] The most treatment method for advanced nasopharyngeal carcinoma was chemoradiation.[4],[5] Recently, some articles showed that the neoadjuvant therapy can improve the survival and decrease the risk of locally recurrence and metastasis.[6]

Neoadjuvant chemotherapy is the administration of chemotherapy agents before a main treatment. Neoadjuvant therapy aims to reduce the size or extent of the cancer before using radical treatment intervention, thus making procedures easier and more likely to succeed, and reducing the consequences of a more extensive treatment technique that would be required if the tumor wasn't reduced in size or extent.

In this study, we included the open published articles about neoadjuvant chemotherapy in the treatment locally advanced nasopharyngeal carcinoma. Moreover, further evaluation of the difference of 5 years overall survival, 5 years disease free survival, recurrence, and metastasis difference between neoadjuvant chemotherapy plus radiation and radiation only by pooling the individual data.


 > Materials and Methods Top


He Xun and Liu Lixian independently electronic searched the Medline and Wanfang database with the text word of nasopharyngeal carcinoma, neoadjuvant chemotherapy, and radiation. The inclusion criteria were: (1) The study types were prospective, randomized controlled trials; (2) the patients were pathology confirmed locally advanced nasopharyngeal carcinoma; (3) the published language was English or Chinese; (4) the patient's treatment modality was neoadjuvant chemotherapy plus radiation versus radiotherapy alone. The author's name, year of publication, chemotherapy and radiation regimen of each study, survival, recurrence, and metastasis data were extracted by two reviewers independently from individual studies.

Statistical analysis

All the data were analyzed by Stata version 11.0 software (http://www.stata.com; Stata Co., College Station, TX, USA). The 5 years survival, 5 years disease free survival, recurrence, and metastasis data were calculated as the odds ratio (OR) with the 95% of confidence interval (CI). The Begg's funnel plot was used to evaluate possible publication bias.


 > Results Top


General characteristics of the included studies

By searching the Medline and Wanfang database, we finally included 5 prospective, randomized controlled trials with 1277 subjects in this meta-analysis. Four studies published in English and other 1 study published in Chinese. The radiation dosage rang for 65–74 Gy for the nasopharynx and 48–50 Gy for the neck. The general characteristics were demonstrated in [Table 1].
Table 1: The general characteristics of included five studies

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Survival analysis

We extracted the 5 years overall survival and 5 years disease free survival data in each individual study. Moreover, the pooled results indicated that 5 years overall survival was not improve in the neoadjuvant chemotherapy followed by radiation in the treatment (OR = 0.84, 95% CI: 0.64–1.05, P > 0.05). Moreover, there was no statistical difference for 5 years disease free survival between the two group (OR = 0.91, 95% CI: 0.78–1.07, P > 0.05) [Figure 1]. The funnel plot was meristic indicating no significant publication bias [Figure 2].
Figure 1: Forest plot for evaluation of 5 years overall survival and disease free survival

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Figure 2: Funnel plot for evaluation of publication bias of 5 years overall survival and disease free survival

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Recurrence and metastasis

By pooling the recurrence data, we found that the recurrence risk in the neoadjuvant chemotherapy combined the radiation group was significant decreased and compared to radiation group (OR = 0.65, 95% CI: 0.50–0.84, P < 0.05). The combined data also showed that the metastasis risk was also decreased in the neoadjuvant chemotherapy group (OR = 0.58, 95% CI: 0.45–0.75, P < 0.05) [Figure 3]. Moreover, no statistical publication bias was showed in the Begg's funnel plot [Figure 4].
Figure 3: Forest plot for evaluation of recurrence and metastasis

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Figure 4: Funnel plot for evaluation of recurrence and metastasis

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 > Discussion Top


Nasopharynx cancer or nasopharyngeal carcinoma is the most common cancer originating in the nasopharynx, the uppermost region of the pharynx ("throat"), behind the nose where the nasal passages and auditory tubes join the remainder of the upper respiratory tract.[5] The epidemiology study showed nasopharyngeal carcinoma is vastly more common in certain regions of the East Asia and Africa than elsewhere, with viral, dietary, and genetic factors implicated in its causation.[3],[12]

Generally, nasopharyngeal carcinoma can be treated by surgery, chemotherapy, or radiotherapy.[13] Moreover, the expression of Epstein–Barr virus latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies. For locally advanced nasopharyngeal carcinoma the radiation therapy is the main method for treatment modality. Recently, several articles reported the neoadjuvant chemotherapy with relative good prognosis.[9],[14] But with a small number of cases included in each individual study, the conclusion was not inconclusive. Theoretically, the neoadjuvant therapy can acts on the micrometastatic disease. The downstaging is then a surrogate marker of efficacy on undetected dissemination, resulting in improved longtime survival compared to the radiation only. The use of neoadjuvant chemotherapy can turn a tumor from untreatable to treatable by shrinking the volume. Often it can be unclear which surrounding structures are directly involved in the disease and which are just showing the signs of inflammation. But, not all the patients are suitable for neoadjuvant chemotherapy because of its extremely toxic.

In this meta-analysis, we included 5 prospective, randomized controlled trials which comparing the efficacy of neoadjuvant chemotherapy plus radiation and radiation. The results indicated that the 5 years overall survival and disease free survival were not improved by adding the neoadjuvant chemotherapy (P > 0.05). But the recurrence and metastasis risk were significantly decreased by adding the neoadjuvant chemotherapy (P < 0.05). Hence, inclusion, we believe that neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in patients with locally advanced nasopharyngeal carcinoma. But with a small number of publication papers included in this meta-analysis, further multiple center prospective, randomized controlled trials is needed to further evaluate the clinical efficacy and toxicity of neoadjuvant chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 1
    
2.
Zheng XH, Lu LX, Li XZ, Jia WH. Quantification of Epstein-Barr virus DNA load in nasopharyngeal brushing samples in the diagnosis of nasopharyngeal carcinoma in southern China. Cancer Sci 2015;6:1-6.  Back to cited text no. 2
    
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Zhang LF, Li YH, Xie SH, Ling W, Chen SH, Liu Q, et al. Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County, Guangdong Province, South China: An age-period-cohort analysis. Chin J Cancer 2015;34:15.  Back to cited text no. 3
    
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Kamran SC, Riaz N, Lee N. Nasopharyngeal carcinoma. Surg Oncol Clin N Am 2015;24:547-61.  Back to cited text no. 4
    
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Petersson F. Nasopharyngeal carcinoma: A review. Semin Diagn Pathol 2015;32:54-73.  Back to cited text no. 5
    
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Lin JC, Jan JS, Hsu CY, Jiang RS, Wang WY. Outpatient weekly neoadjuvant chemotherapy followed by radiotherapy for advanced nasopharyngeal carcinoma: High complete response and low toxicity rates. Br J Cancer 2003;88:187-94.  Back to cited text no. 6
    
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International Nasopharynx Cancer Study Group; VUMCA I Trial. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: A positive effect on progression-free survival. Int J Radiat Oncol Biol Phys 1996;35:463-9.  Back to cited text no. 7
    
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Chua DT, Sham JS, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S, et al. Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group. Cancer 1998;83:2270-83.  Back to cited text no. 8
    
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Ma J, Mai HQ, Hong MH, Min HQ, Mao ZD, Cui NJ, et al. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2001;19:1350-7.  Back to cited text no. 9
    
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Hareyama M, Sakata K, Shirato H, Nishioka T, Nishio M, Suzuki K, et al. A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma. Cancer 2002;94:2217-23.  Back to cited text no. 10
    
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Hongmei Y, Youwang Z, Chaosu H, Yongru W, Shengzhong W. Chemotherapy adjunctive to definitive radiotherapy in locally advanced nasopharyngeal carcinoma (NPC): Prospective randomized study. China Oncol 2003;13:563-6.  Back to cited text no. 11
    
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Xu ZJ, Zheng RS, Zhang SW, Zou XN, Chen WQ. Nasopharyngeal carcinoma incidence and mortality in China in 2009. Chin J Cancer 2013;32:453-60.  Back to cited text no. 12
    
13.
Hutajulu SH, Kurnianda J, Tan IB, Middeldorp JM. Therapeutic implications of Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma. Ther Clin Risk Manag 2014;10:721-36.  Back to cited text no. 13
    
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Rui S, Shaoxiong W, Yun Z, Tiantian C, Meiling D. Evaluation of effect of induction chemotherapy followed by radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. J Oncol 2007;13:372-6.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

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