2014, Number 2
<< Back Next >>
Biotecnol Apl 2014; 31 (2)
Nimotuzumab, effective immunotherapy for the treatment of malignant epithelial tumors
Saurez-Martínez G, Bencomo-Yanes A
Language: Spanish
References: 57
Page: 150-158
PDF size: 874.24 Kb.
ABSTRACT
Nimotuzumab, a humanized monoclonal antibody, is a novel drug against the epidermal growth factor receptor, which is a protein that is highly expressed in malignant tumors of epithelial origin. This paper presents its physicochemical and pharmaceutical characteristics, the results of pre-clinical and clinical research, and the international regulations for the diseases for which its use has been indicated: in advanced head and neck tumors, malignant brain tumors in adults and children, and advanced esophagus tumors. Its safety profile, efficacy and effectiveness studied before and after its regulatory approval are also described. Finally, recommendations are given for its dosage according to clinical evidence, for the appropriate therapeutic use of this medication.
REFERENCES
Cohen S. Isolation of a mouse submaxillary gland protein accelerating in- cisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962; 237:1555-62.
Cowley GP, Smith JA, Gusterson BA. Increased EGF receptors on human squamous carcinoma cell lines. Br J Cancer. 1986;53(2):223-9.
Ciardiello F, Tortora G. Epidermal growth factor receptor (EGFR) as a target in cancer therapy: understanding the role of receptor expression and other molecular determinants that could influence the response to anti-EGFR drugs. Eur J Cancer. 2003;39(10):1348-54.
Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene. 2000;19(56):6550-65.
Cohen EE. Role of epidermal growth factor receptor pathway-targeted therapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2006;24(17):2659-65.
Agulnik M. New approaches to EGFR inhibition for locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN). Med Oncol. 2012; 29(4):2481-91.
Mateo C, Moreno E, Amour K, Lombardero J, Harris W, Perez R. Humanization of a mouse monoclonal antibody that blocks the epidermal growth factor receptor: recovery of antagonistic activity. Immunotechnology. 1997;3(1):71-81.
Prieto Y, Rojas L, Hinojosa L, González I, Aguiar D, de la Luz K, et al. Towards the molecular characterization of the stable producer phenotype of recombinant antibody- producing NS0 myeloma cells. Cytotechnology. 2011;63(4):351-62.
Crombet-Ramos T, Rak J, Perez R, Viloria-Petit A. Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: A humanized anti-EGFR antibody. Int J Cancer. 2002;101(6):567-75.
Crombet T, Osorio M, Cruz T, Roca C, del Castillo R, Mon R, et al. Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol. 2004; 22(9):1646-54.
Crombet T, Pérez R, Lage A, Osorio M, Cruz T. Anticuerpo monoclonal humanizado h-R3: un nuevo concepto terapéutico para el tratamiento del cáncer avanzado. Biotecnol Apl. 2003;20(1):33-51.
Diaz Miqueli A, Blanco R, Garcia B, Badia T, Batista AE, Alonso R, et al. Biological activity in vitro of anti-epidermal growth factor receptor monoclonal antibodies with different affinities. Hybridoma. 2007;26(6):423-31.
Diaz Miqueli A, Rolff J, Lemm M, Fichtner I, Perez R, Montero E. Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies. Br J Cancer. 2009; 100(6):950-8.
Akashi Y, Okamoto I, Iwasa T, Yoshida T, Suzuki M, Hatashita E, et al. Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status. Br J Cancer. 2008; 98(4):749-55.
Basavaraj C, Sierra P, Shivu J, Melarkode R, Montero E, Nair P. Nimotuzumab with chemoradiation confers a survival advantage in treatment-naive head and neck tumors over expressing EGFR. Cancer Biol Ther. 2010;10(7):673-81.
Rodriguez MO, Rivero TC, del Castillo Bahi R, Muchuli CR, Bilbao MA, Vinageras EN, et al. Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck. Cancer Biol Ther. 2010;9(5):343-9.
Rojo F, Gracias E, Villena N, Cruz T, Corominas JM, Corradino I, et al. Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck: a SENDO Foundation study. Clin Cancer Res. 2010;16(8): 2474-82.
Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. mAbs. 2009;1(1):41-8.
Hong J, Peng Y, Liao Y, Jiang W, Wei R, Huo L, et al. Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab. Exp Ther Med. 2012;4(1):151-7.
Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, et al. Treatment of malignant, nonresectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther. 2012;13(8): 600-5.
Solomon MT, Selva JC, Figueredo J, Vaquer J, Toledo C, Quintanal N, et al. Radiotherapy plus the anti-EGFR mAb nimotuzumab or placebo for the treatment of high-grade glioma patients [Abstract]. J Clin Oncol. 2012;30(suppl):2515.
Zhao XY, Guo Y, Zhu YX, Wang Y, Zhu GP, Hu CS, et al. Clinical analysis of nimotuzumab plus cisplatin and fluorouracil regimen as induction treatment in resectable head and neck squamous cell carcinoma. Chinese J Otorhinolaryngol Head Neck Surg. 2012;47(7):536-9.
Crombet T, Torres L, Neninger E, Catala M, Solano ME, Perera A, et al. Pharmacological evaluation of humanized anti-epidermal growth factor receptor, monoclonal antibody h-R3, in patients with advanced epithelial-derived cancer. J Immunother. 2003;26(2):139-48.
Bode U, Massimino M, Bach F, Zimmermann M, Khuhlaeva E, Westphal M, et al. Nimotuzumab treatment of malignant gliomas. Expert Opin Biol Ther. 2012;12(12): 1649-59.
Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos. Registro sanitario de medicamentos. La Habana: Cecmed. c2012[cited 2013 Dec 4]. Available from: http://www. cecmed.cu/Pages/RegSan.htm
Meng J, Gu QP, Meng QF, Zhang J, Li ZP, Si YM, et al. Efficacy of nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen in treatment of advanced oral carcinoma. Cell Biochem Biophys. 2014;68(1):181-4.
Cabanas R, Saurez G, Rios M, Alert J, Reyes A, Valdes J, et al. Treatment of children with high grade glioma with nimotuzumab: a 5-year institutional experience. mAbs. 2013;5(2):202-7.
Yan S, Jiang X, Yang J, Yan D, Wang YX. Radiotherapy for nasopharyngeal carcinoma and combined capecitabine and nimotuzumab treatment for lung metastases in a liver transplantation recipient: a case experience of sustained complete response. Cancer Biother Radiopharm. 2012; 27(8):519-23.
Qi DL, Wang HQ, Li Y, Huang CB, Wang QS, Xu L, et al. Efficacy and adverse effets of nimotuzumab plus palitaxel liposome and carboplatin in the treatment for advanced non-small cell lung cancer. Chinese J Oncol. 2012;34(2):152-5.
Li LF, Wang HQ, Liu XM, Zhang HL, Qiu LH, Qian ZZ, et al. Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer. Chinese J Oncol. 2011;33(8):626-8.
Ling Y, Chen J, Tao M, Chu X, Zhang X. A pilot study of nimotuzumab combined with cisplatin and 5-FU in patients with advanced esophageal squamous cell carcinoma. J Thorac Dis. 2012;4(1):58-62.
Verduzco-Rodriguez L, Aguirre-Gonzalez EH, Verduzco-Aguirre HC. Durable complete response induced by paclitaxelnimotuzumab- methotrexate chemotherapy in a patient with metastatic head and neck squamous cell carcinoma. Hematol Oncol Stem Cell Ther. 2011;4(4):182-4.
Zhao KL, Hu XC, Wu XH, Fu XL, Fan M, Jiang GL. A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus. Invest New Drugs. 2012;30(4):1585-90.
Winquist E, Nabid A, Sicheri D, Ganguly P, Venkatesan V, Schneider K, et al. A phase I dose escalation study of a humanized monoclonal antibody to EGFR (hR3) in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) treated with radiotherapy (RT) [Abstract]. Proc Am Soc Clin Oncol. 2002;21:91a.
Huang XD, Yi JL, Gao L, Xu GZ, Jin J, Yang WZ, et al. Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Zhonghua Zhong Liu Za Zhi. 2007;29(3): 197-201.
Babu K, Joseph B, Vidyasagar MS, Bonanthaya R, Pasha CT, Bapsy PP, et al: An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): Four-year survival results from a phase IIb study [Abstract]. J Clin Oncol 2010;28(15 Suppl):428s.
Piedra P, Morejón O. Report of the Fifth Nimotuzumab Global Meeting. Biotecnol Apl. 2010;27(1):56-61.
Piedra P, Saurez G, Barroso M, Ledón N. Observational clinical study in patients with advanced stage epithelial tumors treated with nimotuzumab [Abstract]. Can J Clin Pharmacol. 2010;17(1):e234.
Fuller GN, Scheithauer BW. The 2007 Revised World Health Organization (WHO) Classification of Tumours of the Central Nervous System: newly codified entities. Brain Pathol. 2007;17(3):304-7.
Lorenzoni J, Torrico A, Villanueva P, Gederlini A, Torrealba G. Surgery for high-grade gliomas in a developing country: survival estimation using a simple stratification system. Surg Neurol. 2008; 70(6):591-7; discussion 7.
Ramos TC, Figueredo J, Catala M, Gonzalez S, Selva JC, Cruz TM, et al. Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor (EGFR) antibody h-R3: report from a phase I/II trial. Cancer Biol Ther. 2006;5(4):375-9.
Westphal M, Bach F. Final results of a randomized phase III trial of nimotuzumab for the treatment of newly diagnosed glioblastoma in addition to standard radiation and chemotherapy with temozolomide versus standard radiation and temoziolamide. J Clin Oncol. 2012;30(15 suppl 1):2033.
Centro de Inmunología Molecular. Estudio de toxicidad local de nimotuzumab en conejos. La Habana: Centro de Investigación de Evaluaciones Biológicas (CIEB); 1997.
Packer RJ. Progress and challenges in childhood brain tumors. J Neurooncol. 2005;75(3):239-42.
Saurez G, Cabanas R, Zaldivar M, Garnier T, Iglesias B, Piedra P, et al. Clinical experience with nimotuzumab in cuban pediatric patients with brain tumors, 2005 to 2007. MEDICC Rev. 2009;11(3):27-33.
Massimino M, Bode U, Biassoni V, Fleischhack G. Nimotuzumab for pediatric diffuse intrinsic pontine gliomas. Expert Opin Biol Ther. 2011;11(2):247-56.
Wong RK, Malthaner RA, Zuraw L, Rumble RB, Cancer Care Ontario Practice Guidelines Initiative Gastrointestinal Cancer Disease Site G. Combined modality radiotherapy and chemotherapy in nonsurgical management of localized carcinoma of the esophagus: a practice guideline. Int J Radiat Oncol Biol Phys. 2003;55(4):930-42.
Castro G, Segalla J, Stümoller C, Schmerling R, Andrade CJ, Pinczowski H, et al. Complete response (CR) to nimotuzumab plus chemoradiation in locally advanced esophageal cancer: Preliminary results of an ongoing randomized trial. Ann Oncol. 2010;21 Suppl. 8: viii260.
Saurez G. Reporte del Séptimo encuentro científico internacional: Nimo–meeting 2012 en la sesión de tumores cerebrales. Rev Cubana Neurol Neurocir. 2012;2(2):171-6.
Boland W, Bebb G. The emerging role of nimotuzumab in the treatment of non-small cell lung cancer. Biologics. 2010;4:289-98.
Kim SH, Shim HS, Cho J, Jeong JH, Kim SM, Hong YK, et al. A phase I trial of gefitinib and nimotuzumab in patients with advanced non-small cell lung cancer (NSCLC). Lung Cancer. 2013;79(3):270-5.
World Health Organization. International Clinical Trials Registry Platform (ICTRP). c2013.Geneva: WHO [cited 2013 Dec 4]. Available from:http://apps.who.int/ictrp/search/ en/
Arteaga ME, Ledon N, Casaco A, Pardo B, Garcia M, Boleda M, et al. Systemic and skin toxicity in Cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti- epidermal growth factor receptor monoclonal antibody Nimotuzumab. Cancer Biol Ther. 2007;6(9): 1390-5.
Arteaga-Perez ME, Maceira M, Casaco A, Hernandez-Sosa O, Bada-Barro AM, Leon-Goni A, et al. Multiple dose toxicity study of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 intravenously administered to Cercopithecus aethiops sabaeus monkeys. Hum Exp Toxicol. 2004;23(5):219-27.
Cimaher (nimotuzumab). Resumen de las características del producto. Habana: CIMAB S.A. c2013 [cited 2013 Dec 4]. Available from: http:// www.cecmed.cu/Pages/RCP_ Med.htm
Boland WK, Bebb G. Nimotuzumab: a novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity. Expert Opin Biol Ther. 2009;9(9):1199-206.
Garrido G, Tikhomirov IA, Rabasa A, Yang E, Gracia E, Iznaga N, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther. 2011;11(4):373-82.