Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis

Zhi-Gang Liu, Yu Zhao, Jiao Tang, Yu-Juan Zhou, Wen-Juan Yang, Yan-Fang Qiu, Hui Wang, Zhi-Gang Liu, Yu Zhao, Jiao Tang, Yu-Juan Zhou, Wen-Juan Yang, Yan-Fang Qiu, Hui Wang

Abstract

Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated.

Keywords: EGFR; NPC; chemoradiotherapy; nimotuzumab.

Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1. Kaplan–Meier estimates of local recurrence…
Figure 1. Kaplan–Meier estimates of local recurrence free survival
A. distant metastasis free survival B. and overall survival C.

References

    1. 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.
    1. Zhang ZC, Fu S, Wang F, Wang HY, Zeng YX, Shao JY. Oncogene mutational profile in nasopharyngeal carcinoma. OncoTargets and therapy. 2014;7:457–467.
    1. Chua DT, Ma J, Sham JS, Mai HQ, Choy DT, Hong MH, Lu TX, Min HQ. Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials. J Clin Oncol. 2005;23:1118–1124.
    1. Reddy BK, Lokesh V, Vidyasagar MS, Shenoy K, Babu KG, Shenoy A, Naveen T, Joseph B, Bonanthaya R, Nanjundappa, Bapsy PP, Loknatha, Shetty J, Prasad K, Tanvir Pasha CR. Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients. Oral oncology. 2014;50:498–505.
    1. Dorsey K, Agulnik M. Promising new molecular targeted therapies in head and neck cancer. Drugs. 2013;73:315–325.
    1. Kohler J, Schuler M. Afatinib, erlotinib and gefitinib in the first-line therapy of EGFR mutation-positive lung adenocarcinoma: a review. Onkologie. 2013;36:510–518.
    1. Prenen H, Vecchione L, Van Cutsem E. Role of targeted agents in metastatic colorectal cancer. Targeted oncology. 2013;8:83–96.
    1. Yewale C, Baradia D, Vhora I, Patil S, Misra A. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013;34:8690–8707.
    1. Feng HX, Guo SP, Li GR, Zhong WH, Chen L, Huang LR, Qin HY. Toxicity of concurrent chemoradiotherapy with cetuximab for locoregionally advanced nasopharyngeal carcinoma. Medical oncology (Northwood, London, England) 2014;31:170.
    1. Talavera A, Friemann R, Gomez-Puerta S, Martinez-Fleites C, Garrido G, Rabasa A, Lopez-Requena A, Pupo A, Johansen RF, Sanchez O, Krengel U, Moreno E. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer research. 2009;69:5851–5859.
    1. Crombet T, Torres L, Neninger E, Catala M, Solano ME, Perera A, Torres O, Iznaga N, Torres F, Perez R, Lage A. Pharmacological evaluation of humanized anti-epidermal growth factor receptor, monoclonal antibody h-R3, in patients with advanced epithelial-derived cancer. Journal of immunotherapy (Hagerstown, Md : 1997) 2003;26:139–148.
    1. Du F, Zheng Z, Shi S, Jiang Z, Qu T, Yuan X, Sun Y, Song Y, Yang L, Zhao J, Wang J, Chi Y. S-1 and Cisplatin With or Without Nimotuzumab for Patients With Untreated Unresectable or Metastatic Gastric Cancer: A Randomized, Open-Label Phase 2 Trial. Medicine. 2015;94:e958.
    1. Solomon MT, Miranda N, Jorrin E, Chon I, Marinello JJ, Alert J, Lorenzo-Luaces P, Crombet T. Nimotuzumab in combination with radiotherapy in high grade glioma patients: a single institution experience. Cancer biology & therapy. 2014;15:504–509.
    1. Zhang P, Wu SK, Wang Y, Fan ZX, Li CR, Feng M, Xu P, Wang WD, Lang JY. p53, MDM2, eIF4E and EGFR expression in nasopharyngeal carcinoma and their correlation with clinicopathological characteristics and prognosis: A retrospective study. Oncology letters. 2015;9:113–118.
    1. Gonzalez JE, Barquinero JF, Lee M, Garcia O, Casaco A. Radiosensitization induced by the anti-epidermal growth factor receptor monoclonal antibodies cetuximab and nimotuzumab in A431 cells. Cancer biology & therapy. 2012;13:71–76.
    1. Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, Arvind AS. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. mAbs. 2009;1:41–48.
    1. Jin T, Zhu Y, Luo JL, Zhou N, Li DC, Ju HX, Fan YT, Liu Y, Zhu YP, Feng HY, Liu LY. Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer. International journal of colorectal disease. 2015;30:337–345.
    1. Zhang X, Wang J, Wu W, Liu M, Zhao F, Du L, Huang D, Yang S, Ma L. Efficacy and safety of combined radiotherapy with EGFR inhibitors and chemotherapy for laryngeal organ preservation in patients with locally advanced hypopharyngeal carcinomas. Current cancer drug targets. 2014;14:589–598.
    1. Hong J, Peng Y, Liao Y, Jiang W, Wei R, Huo L, Han Z, Duan C, Zhong M. Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab. Experimental and therapeutic medicine. 2012;4:151–157.
    1. Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, Hernadez IM, Albuerne YA, Moreno BP, Alvarez ES, Callejo IP, Alert J, Martell JA, Gonzalez YS, Gonzalez YS, Astudillo de la Vega H, et al. 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 biology & therapy. 2012;13:600–605.
    1. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. The New England journal of medicine. 2006;354:567–578.
    1. Saleh-Ebrahimi L, Zwicker F, Muenter MW, Bischof M, Lindel K, Debus J, Huber PE, Roeder F. Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer - a retrospective single center analysis. Radiation oncology (London, England) 2013;8:20.
    1. James R, Vishwakarma S, Chivukula IV, Basavaraj C, Melarkode R, Montero E, Nair P. EGFR targeting monoclonal antibody combines with an mTOR inhibitor and potentiates tumor inhibition by acting on complementary signaling hubs. Cancer Med. 2012;1:114–127.
    1. Song H, Pan B, Yi J, Chen L. Featured article: autophagic activation with nimotuzumab enhanced chemosensitivity and radiosensitivity of esophageal squamous cell carcinoma. Experimental biology and medicine (Maywood, NJ) 2014;239:529–541.
    1. Zhao L, Li QQ, Zhang R, Xi M, Liao YJ, Qian D, He LR, Zeng YX, Xie D, Liu MZ. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumour Biol. 2012;33:1115–1123.
    1. Zhao L, He LR, Xi M, Cai MY, Shen JX, Li QQ, Liao YJ, Qian D, Feng ZZ, Zeng YX, Xie D, Liu MZ. Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3. Journal of translational medicine. 2012;10:249.
    1. Diaz Miqueli A, Blanco R, Garcia B, Badia T, Batista AE, Alonso R, Montero E. Biological activity in vitro of anti-epidermal growth factor receptor monoclonal antibodies with different affinities. Hybridoma (2005) 2007;26:423–431.

Source: PubMed

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