尼妥珠单抗联合放射治疗对胶质瘤效果的探究
An Investigation of the Effect of Nimotuzumab Combined with Radiation Therapy on Gliomas
DOI: 10.12677/acm.2025.1541276, PDF,   
作者: 张巍瀚：内蒙古医科大学第一临床医学院，内蒙古 呼和浩特；闫文明*：内蒙古医科大学附属医院放疗科，内蒙古 呼和浩特
关键词: 尼妥珠单抗；胶质瘤；放射治疗；靶向药物；Nimotuzumab； Gliomas； Radiation Therapy； Targeted Drug
摘要: 源自神经上皮的肿瘤统称为脑胶质瘤，占颅脑肿瘤的40%~50%，是最常见的原发性颅内肿瘤。年发病率为3~8人/10万人。尼妥珠单抗是一种人源化单克隆抗体，可特异性结合人表皮生长因子受体，阻断受体激活。其放射增敏能力的证据已得到广泛评估。本文整合了已发表的关于尼妥珠单抗在成人和儿童人群中结合放疗或放化疗治疗神经胶质瘤的作用的研究结果。首先，回顾了尼妥珠单抗的作用机制及其目前在包含放疗和化放疗的临床试验中的应用。其次，给出了在实验环境中驱动尼妥珠单抗放射增敏的潜在机制的综合解释。最后，基于尼妥珠单抗有利的毒性特征，提出了表皮生长因子受体靶向结合放疗方案的未来方向。希望这篇综述可以为合理设计尼妥珠单抗作为胶质瘤治疗的新方法提供进一步的见解。
Abstract: Tumors originating from neuroepithelium are collectively called gliomas, accounting for 40%~50% of brain tumors, and are the most common primary intracranial tumors. The annual incidence rate is 3~8 people/100,000 people. Nimotuzumab is a humanized monoclonal antibody, which can specifically bind to human epidermal growth factor receptor and block its activation. The evidence of its radiosensitizing ability has been widely evaluated. This paper integrates the published research results about the effect of nimotuzumab combined with radiotherapy or chemoradiotherapy in the treatment of glioma in adults and children. Firstly, the mechanism of nimotuzumab and its current application in clinical trials including radiotherapy and chemotherapy were reviewed. Secondly, a comprehensive explanation of the potential mechanism driving nimotuzumab radiosensitization in the experimental environment is given. Finally, based on the favorable toxicity characteristics of nimotuzumab, the future direction of targeted combination of epidermal growth factor receptor and radiotherapy was put forward. It is hoped that this review can provide further insights for the rational design of nimotuzumab as a new treatment for glioma.
文章引用：张巍瀚, 闫文明. 尼妥珠单抗联合放射治疗对胶质瘤效果的探究[J]. 临床医学进展, 2025, 15(4): 3098-3108. https://doi.org/10.12677/acm.2025.1541276

参考文献

[1] Louis, D.N., Ohgaki, H., Wiestler, O.D., Cavenee, W.K., Burger, P.C., Jouvet, A., et al. (2007) The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica, 114, 97-109. [Google Scholar] [CrossRef] [PubMed]
[2] Laperriere, N., Zuraw, L. and Cairncross, G. (2002) Radiotherapy for Newly Diagnosed Malignant Glioma in Adults: A Systematic Review. Radiotherapy and Oncology, 64, 259-273. [Google Scholar] [CrossRef] [PubMed]
[3] Hart, M.G., Grant, R., Garside, R., Rogers, G., Somerville, M. and Stein, K. (2008) Temozolomide for High Grade Glioma [Review]. Cochrane Database of Systematic Reviews, 2008, CD007415.
[4] Koshy, M., Villano, J.L., Dolecek, T.A., Howard, A., Mahmood, U., Chmura, S.J., et al. (2011) Improved Survival Time Trends for Glioblastoma Using the SEER 17 Population-Based Registries. Journal of Neuro-Oncology, 107, 207-212. [Google Scholar] [CrossRef] [PubMed]
[5] Nazzaro, J.M. and Neuwelt, E.A. (1990) The Role of Surgery in the Management of Supratentorial Intermediate and High-Grade Astrocytomas in Adults. Journal of Neurosurgery, 73, 331-344. [Google Scholar] [CrossRef] [PubMed]
[6] Wild-Bode, C., Weller, M., Rimner, A., Dichgans, J. and Wick, W. (2001) Sublethal Irradiation Promotes Migration and Invasiveness of Glioma Cells: Implications for Radiotherapy of Human Glioblastoma. Cancer Research, 61, 2744-2750.
[7] Garden, A.S., Maor, M.H., Alfred Yung, W.K., Bruner, J.M., Woo, S.Y., Moser, R.P., et al. (1991) Outcome and Patterns of Failure Following Limited-Volume Irradiation for Malignant Astrocytomas. Radiotherapy and Oncology, 20, 99-110. [Google Scholar] [CrossRef] [PubMed]
[8] Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., et al. (2006) Glioma Stem Cells Promote Radioresistance by Preferential Activation of the DNA Damage Response. Nature, 444, 756-760. [Google Scholar] [CrossRef] [PubMed]
[9] Ciardiello, F. and Tortora, G. (2008) EGFR Antagonists in Cancer Treatment. New England Journal of Medicine, 358, 1160-1174. [Google Scholar] [CrossRef] [PubMed]
[10] Hennequin, C., Quero, L. and Favaudon, V. (2008) Déterminants et facteurs prédictifs pour la radiosensibilité tumorale. Cancer/Radiothérapie, 12, 3-13. [Google Scholar] [CrossRef] [PubMed]
[11] Stupp, R., Mason, W.P., van den Bent, M.J., Weller, M., Fisher, B., Taphoorn, M.J.B., et al. (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine, 352, 987-996. [Google Scholar] [CrossRef] [PubMed]
[12] Lorenzoni, J., Torrico, A., Villanueva, P., Gederlini, A. and Torrealba, G. (2008) Surgery for High-Grade Gliomas in a Developing Country: Survival Estimation Using a Simple Stratification System. Surgical Neurology, 70, 591-597. [Google Scholar] [CrossRef] [PubMed]
[13] Weller, M., Stupp, R., Reifenberger, G., Brandes, A.A., van den Bent, M.J., Wick, W., et al. (2009) MGMT Promoter Methylation in Malignant Gliomas: Ready for Personalized Medicine? Nature Reviews Neurology, 6, 39-51. [Google Scholar] [CrossRef] [PubMed]
[14] Yabroff, K.R., Harlan, L., Zeruto, C., Abrams, J. and Mann, B. (2012) Patterns of Care and Survival for Patients with Glioblastoma Multiforme Diagnosed during 2006. Neuro-Oncology, 14, 351-359. [Google Scholar] [CrossRef] [PubMed]
[15] Zawlik, I., Vaccarella, S., Kita, D., Mittelbronn, M., Franceschi, S. and Ohgaki, H. (2008) Promoter Methylation and Polymorphisms of The Mgmt Gene in Glioblastomas: A Population-Based Study. Neuroepidemiology, 32, 21-29. [Google Scholar] [CrossRef] [PubMed]
[16] Stupp, R., Mayer, M., Kann, R., Weder, W., Zouhair, A., Betticher, D.C., et al. (2009) Neoadjuvant Chemotherapy and Radiotherapy Followed by Surgery in Selected Patients with Stage IIIB Non-Small-Cell Lung Cancer: A Multicentre Phase II Trial. The Lancet Oncology, 10, 785-793. [Google Scholar] [CrossRef] [PubMed]
[17] Sartor, C.I. (2004) Mechanisms of Disease: Radiosensitization by Epidermal Growth Factor Receptor Inhibitors. Nature Clinical Practice Oncology, 1, 80-87. [Google Scholar] [CrossRef] [PubMed]
[18] Viana-Pereira, M., Lopes, J.M., Little, S., et al. (2008) Analysis of EGFR Overexpression, EGFR Gene Amplification and the EG-FRvIII Mutation in Portuguese High-Grade Gliomas. Anticancer Research, 28, 913-920.
[19] Bredel, M., Pollack, I.F., Hamilton, R.L. and James, C.D. (1999) Epidermal Growth Factor Receptor Expression and Gene Amplification in High-Grade Non-Brainstem Gliomas of Childhood. Clinical Cancer Research, 5, 1786-1792.
[20] Mellinghoff, I.K., Wang, M.Y., Vivanco, I., Haas-Kogan, D.A., Zhu, S., Dia, E.Q., et al. (2005) Molecular Determinants of the Response of Glioblastomas to EGFR Kinase Inhibitors. New England Journal of Medicine, 353, 2012-2024. [Google Scholar] [CrossRef] [PubMed]
[21] Gilbertson, R.J., Hill, D.A., Hernan, R., et al. (2003) ERBB1 Is Amplified and Overexpressed in High-Grade Diffusely Infiltrative Pediatric Brain Stem Glioma. Clinical Cancer Research, 9, 3620-3624.
[22] Yarden, Y. and Pines, G. (2012) The ERBB Network: At Last, Cancer Therapy Meets Systems Biology. Nature Reviews Cancer, 12, 553-563. [Google Scholar] [CrossRef] [PubMed]
[23] Brennan, C.W., Verhaak, R.G.W., McKenna, A., Campos, B., Noushmehr, H., Salama, S.R., et al. (2013) The Somatic Genomic Landscape of Glioblastoma. Cell, 155, 462-477. [Google Scholar] [CrossRef] [PubMed]
[24] Rude Voldborg, B., Damstrup, L., Spang-Thomsen, M. and Skovgaard Poulsen, H. (1997) Epidermal Growth Factor Receptor (EGFR) and EGFR Mutations, Function and Possible Role in Clinical Trials. Annals of Oncology, 8, 1197-1206. [Google Scholar] [CrossRef] [PubMed]
[25] Sepúlveda-Sánchez, J.M., Vaz, M.Á., Balañá, C., Gil-Gil, M., Reynés, G., Gallego, Ó., et al. (2017) Phase II Trial of Dacomitinib, a Pan-human EGFR Tyrosine Kinase Inhibitor, in Recurrent Glioblastoma Patients with EGFR Amplification. Neuro-Oncology, 19, 1522-1531. [Google Scholar] [CrossRef] [PubMed]
[26] Byeon, S., Hong, J.Y., Lee, J., Nam, D., Park, S.H., Park, J.O., et al. (2020) Use of Gefitinib in EGFR-Amplified Refractory Solid Tumors: An Open-Label, Single-Arm, Single-Center Prospective Pilot Study. Targeted Oncology, 15, 185-192. [Google Scholar] [CrossRef] [PubMed]
[27] Warren, K.E. (2012) Diffuse Intrinsic Pontine Glioma: Poised for Progress. Frontiers in Oncology, 2, Article No. 205. [Google Scholar] [CrossRef] [PubMed]
[28] Massimino, M., Biassoni, V., Miceli, R., Schiavello, E., Warmuth-Metz, M., Modena, P., et al. (2014) Results of Nimotuzumab and Vinorelbine, Radiation and Re-Irradiation for Diffuse Pontine Glioma in Childhood. Journal of Neuro-Oncology, 118, 305-312. [Google Scholar] [CrossRef] [PubMed]
[29] McVeigh, L., Patel, T., Miclea, M., Schwark, K., Ajaero, D., Momen, F., et al. (2025) Updates in Diagnostic Techniques and Experimental Therapies for Diffuse Intrinsic Pontine Glioma. Cancers, 17, Article No. 931. [Google Scholar] [CrossRef] [PubMed]
[30] Jovanovich, N., Habib, A., Head, J., Hameed, F., Agnihotri, S. and Zinn, P.O. (2023) Pediatric Diffuse Midline Glioma: Understanding the Mechanisms and Assessing the Next Generation of Personalized Therapeutics. Neuro-Oncology Advances, 5, vdad040. [Google Scholar] [CrossRef] [PubMed]
[31] Arms, L.M., Duchatel, R.J., Jackson, E.R., Sobrinho, P.G., Dun, M.D. and Hua, S. (2024) Current Status and Advances to Improving Drug Delivery in Diffuse Intrinsic Pontine Glioma. Journal of Controlled Release, 370, 835-865. [Google Scholar] [CrossRef] [PubMed]
[32] Mehta, A.M., Sonabend, A.M. and Bruce, J.N. (2017) Convection-Enhanced Delivery. Neurotherapeutics, 14, 358-371. [Google Scholar] [CrossRef] [PubMed]
[33] Vanan, M.I. and Eisenstat, D.D. (2015) DIPG in Children—What Can We Learn from the Past? Frontiers in Oncology, 5, Article No. 237. [Google Scholar] [CrossRef] [PubMed]
[34] Morales La Madrid, A., Hashizume, R. and Kieran, M.W. (2015) Future Clinical Trials in DIPG: Bringing Epigenetics to the Clinic. Frontiers in Oncology, 5, Article No. 148. [Google Scholar] [CrossRef] [PubMed]
[35] Mateo, C., Moreno, E., Amour, K., Lombardero, J., Harris, W. and érez, R. (1997) Humanization of a Mouse Monoclonal Antibody That Blocks the Epidermal Growth Factor Receptor: Recovery of Antagonistic Activity. Immunotechnology, 3, 71-81. [Google Scholar] [CrossRef] [PubMed]
[36] Diaz Miqueli, A., Blanco, R., Garcia, B., Badia, T., Batista, A.E., Alonso, R., et al. (2007) Biological Activity in Vitro of Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies with Different Affinities. Hybridoma, 26, 423-432. [Google Scholar] [CrossRef] [PubMed]
[37] Crombet‐Ramos, T., Rak, J., Pérez, R. and Viloria‐Petit, A. (2002) Antiproliferative, Antiangiogenic and Proapoptotic Activity of H‐r3: A Humanized Anti‐EGFR Antibody. International Journal of Cancer, 101, 567-575. [Google Scholar] [CrossRef] [PubMed]
[38] Viloria-Petit, A., Crombet, T., Jothy, S., et al. (2001) Acquired Resistance to the Antitumor Effect of Epidermal Growth Factor Receptor-Blocking Antibodies in Vivo: A Role for Altered Tumor Angiogenesis. Cancer Research, 61, 5090-5101.
[39] Nathanson, D.A., Gini, B., Mottahedeh, J., Visnyei, K., Koga, T., Gomez, G., et al. (2014) Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA. Science, 343, 72-76. [Google Scholar] [CrossRef] [PubMed]
[40] Crombet, T., Osorio, M., Cruz, T., Roca, C., del Castillo, R., Mon, R., et al. (2004) 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. Journal of Clinical Oncology, 22, 1646-1654. [Google Scholar] [CrossRef] [PubMed]
[41] Rodríguez, M.O., Rivero, T.C., Del Castillo Bahi, R., Muchuli, C.R., Bilbao, M.A., Vinageras, E.N., et al. (2010) Nimotuzumab plus Radiotherapy for Unresectable Squamous-Cell Carcinoma of the Head and Neck. Cancer Biology & Therapy, 9, 343-349. [Google Scholar] [CrossRef] [PubMed]
[42] Crombet Ramos, T., Figueredo, J., Catala, M., Sandra, G., Selva, J.C., Cruz, T.M., et al. (2006) 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 Biology & Therapy, 5, 375-379. [Google Scholar] [CrossRef] [PubMed]
[43] Massimino, M., Bode, U., Biassoni, V. and Fleischhack, G. (2010) Nimotuzumab for Pediatric Diffuse Intrinsic Pontine Gliomas. Expert Opinion on Biological Therapy, 11, 247-256. [Google Scholar] [CrossRef] [PubMed]
[44] Ramos-Suzarte, M., Lorenzo-Luaces, P., Lazo, N.G., Perez, M.L., Soriano, J.L., Gonzalez, C.E.V., et al. (2012) 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, 13, 600-605. [Google Scholar] [CrossRef] [PubMed]
[45] Diaz Miqueli, A., Rolff, J., Lemm, M., Fichtner, I., Perez, R. and Montero, E. (2009) Radiosensitisation of U87MG Brain Tumours by Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies. British Journal of Cancer, 100, 950-958. [Google Scholar] [CrossRef] [PubMed]
[46] Parenrengi, M.A., Suryaningtyas, W., Al Fauzi, A., Hafid Bajamal, A., Kusumastuti, K., Utomo, B., et al. (2022) Nimotuzumab as Additional Therapy for GLIOMA in Pediatric and Adolescent: A Systematic Review. Cancer Control, 29, 2. [Google Scholar] [CrossRef] [PubMed]
[47] Kim, H.J., Lee, J.H., Kim, Y., Lim, D.H., Park, S., Ahn, S.D., et al. (2023) Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study. Cancer Research and Treatment, 55, 41-49. [Google Scholar] [CrossRef] [PubMed]
[48] Akashi, Y., Okamoto, I., Iwasa, T., Yoshida, T., Suzuki, M., Hatashita, E., et al. (2008) 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. British Journal of Cancer, 98, 749-755. [Google Scholar] [CrossRef] [PubMed]
[49] González, J.E., Barquinero, J.F., Lee, M., García, O. and Casacó, A. (2012) Radiosensitization Induced by the Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies Cetuximab and Nimotuzumab in A431 Cells. Cancer Biology & Therapy, 13, 71-76. [Google Scholar] [CrossRef] [PubMed]
[50] Huang, S.M., Bock, J.M. and Harari, P.M. (1999) Epidermal Growth Factor Receptor Blockade with C225 Modulates Proliferation, Apoptosis, and Radiosensitivity in Squamous Cell Carcinomas of the Head and Neck. Cancer Research, 59, 1935-1940.
[51] Dent, P., Reardon, D.B., Park, J.S., Bowers, G., Logsdon, C., Valerie, K., et al. (1999) Radiation-Induced Release of Transforming Growth Factor Α Activates the Epidermal Growth Factor Receptor and Mitogen-Activated Protein Kinase Pathway in Carcinoma Cells, Leading to Increased Proliferation and Protection from Radiation-Induced Cell Death. Molecular Biology of the Cell, 10, 2493-2506. [Google Scholar] [CrossRef] [PubMed]
[52] Shintani, S., Li, C., Mihara, M., Terakado, N., Yano, J., Nakashiro, K., et al. (2003) Enhancement of Tumor Radioresponse by Combined Treatment with Gefitinib (Iressa, ZD1839), an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Is Accompanied by Inhibition of DNA Damage Repair and Cell Growth in Oral Cancer. International Journal of Cancer, 107, 1030-1037. [Google Scholar] [CrossRef] [PubMed]
[53] Liang, K., Ang, K.K., Milas, L., Hunter, N. and Fan, Z. (2003) The Epidermal Growth Factor Receptor Mediates Radioresistance. International Journal of Radiation Oncology Biology Physics, 57, 246-254. [Google Scholar] [CrossRef] [PubMed]
[54] Das, A.K., Chen, B.P., Story, M.D., Sato, M., Minna, J.D., Chen, D.J., et al. (2007) Somatic Mutations in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor (EGFR) Abrogate EGFR-Mediated Radioprotection in Non-Small Cell Lung Carcinoma. Cancer Research, 67, 5267-5274. [Google Scholar] [CrossRef] [PubMed]
[55] Harari, P.M. and Huang, S. (2001) Head and Neck Cancer as a Clinical Model for Molecular Targeting of Therapy: Combining EGFR Blockade with Radiation. International Journal of Radiation Oncology Biology Physics, 49, 427-433. [Google Scholar] [CrossRef] [PubMed]
[56] Nyati, M.K., Maheshwari, D., Hanasoge, S., Sreekumar, A., Rynkiewicz, S.D., Chinnaiyan, A.M., et al. (2004) Radiosensitization by Pan ErbB Inhibitor CI-1033 in Vitro and in Vivo. Clinical Cancer Research, 10, 691-700. [Google Scholar] [CrossRef] [PubMed]
[57] Herbst, R.S., Johnson, D.H., Mininberg, E., Carbone, D.P., Henderson, T., Kim, E.S., et al. (2005) Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination with the Her-1/epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients with Recurrent Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 23, 2544-2555. [Google Scholar] [CrossRef] [PubMed]
[58] Zhao, L., He, L., Xi, M., Cai, M., Shen, J., Li, Q., et al. (2012) Nimotuzumab Promotes Radiosensitivity of EGFR-Overexpression Esophageal Squamous Cell Carcinoma Cells by Upregulating IGFBP-3. Journal of Translational Medicine, 10, Article No. 249. [Google Scholar] [CrossRef] [PubMed]
[59] Yu, Y., Guan, H., Jiang, L., Li, X., Xing, L. and Sun, X. (2020) Nimotuzumab, an EGFR-Targeted Antibody, Promotes Radiosensitivity of Recurrent Esophageal Squamous Cell Carcinoma. International Journal of Oncology, 56, 945-956. [Google Scholar] [CrossRef] [PubMed]
[60] Schmidt-Ullrich, R.K., Mikkelsen, R.B., Dent, P., Todd, D.G., Valerie, K., Kavanagh, B.D., et al. (1997) Radiation-induced Proliferation of the Human A431 Squamous Carcinoma Cells Is Dependent on EGFR Tyrosine Phosphorylation. Oncogene, 15, 1191-1197. [Google Scholar] [CrossRef] [PubMed]
[61] Schmidt-Ullrich, R.K., Valerie, K., Fogleman, P.B. and Walters, J. (1996) Radiation-Induced Autophosphorylation of Epidermal Growth Factor Receptor in Human Malignant Mammary and Squamous Epithelial Cells. Radiation Research, 145, 81-85. [Google Scholar] [CrossRef] [PubMed]
[62] Tabernero, J. (2007) The Role of VEGF and EGFR Inhibition: Implications for Combining Anti-VEGF and Anti-EGFR Agents. Molecular Cancer Research, 5, 203-220. [Google Scholar] [CrossRef] [PubMed]
[63] Niu, G., Wright, K.L., Huang, M., Song, L., Haura, E., Turkson, J., et al. (2002) Constitutive Stat3 Activity Up-Regulates VEGF Expression and Tumor Angiogenesis. Oncogene, 21, 2000-2008. [Google Scholar] [CrossRef] [PubMed]
[64] Schmidt-Ullrich, R.K., Contessa, J.N., Lammering, G., Amorino, G. and Lin, P. (2003) ERBB Receptor Tyrosine Kinases and Cellular Radiation Responses. Oncogene, 22, 5855-5865. [Google Scholar] [CrossRef] [PubMed]
[65] Ramakrishnan, M.S., Eswaraiah, A., Crombet, T., Piedra, P., Saurez, G., Iyer, H., et al. (2009) Nimotuzumab, a Promising Therapeutic Monoclonal for Treatment of Tumors of Epithelial Origin. mAbs, 1, 41-48. [Google Scholar] [CrossRef] [PubMed]
[66] Bebb, G., Smith, C., Rorke, S., Boland, W., Nicacio, L., Sukhoo, R., et al. (2010) Phase I Clinical Trial of the Anti-EGFR Monoclonal Antibody Nimotuzumab with Concurrent External Thoracic Radiotherapy in Canadian Patients Diagnosed with Stage IIb, III or IV Non-Small Cell Lung Cancer Unsuitable for Radical Therapy. Cancer Chemotherapy and Pharmacology, 67, 837-845. [Google Scholar] [CrossRef] [PubMed]
[67] Choi, H.J., Sohn, J.H., Lee, C.G., Shim, H.S., Lee, I., Yang, W.I., et al. (2011) A Phase I Study of Nimotuzumab in Combination with Radiotherapy in Stages IIB-IV Non-Small Cell Lung Cancer Unsuitable for Radical Therapy: Korean Results. Lung Cancer, 71, 55-59. [Google Scholar] [CrossRef] [PubMed]
[68] Bebb, G., Boland, W. and Melosky, B. (2011) Don’t Jump to Rash Conclusions. Cancer Biology & Therapy, 11, 639-641. [Google Scholar] [CrossRef] [PubMed]
[69] Cabanas, R., Saurez, G., Rios, M., Alert, J., Reyes, A., Valdes, J., et al. (2013) Treatment of Children with High Grade Glioma with Nimotuzumab: A 5-Y Institutional Experience. mAbs, 5, 202-207. [Google Scholar] [CrossRef] [PubMed]

为你推荐