Share This Article:

Nimotuzumab with Induction Chemotherapy and Chemo-Radiation in Patients with Advanced Head and Neck Cancer

Abstract Full-Text HTML XML Download Download as PDF (Size:2581KB) PP. 146-152
DOI: 10.4236/jct.2015.62016    3,140 Downloads   3,985 Views   Citations

ABSTRACT

Background: Head and neck squamous cell carcinoma (HNSCC), is a common malignancy in the Indian Population. In locally advanced disease, chemoradiation is the standard of care. Although induction chemotherapy has been much studied, no clear benefit has been identified apart from laryngeal preservation. A few randomized trials have demonstrated improved response rate, disease free survival, and overall survival, with induction chemotherapy. Nimotuzumab is a humanized monoclonal antibody targeting epidermal growth factor receptors (EGFR). Unlike other Anti-EGFR monoclonal antibodies, it is demonstrated to be safer when combined with chemotherapy and/or radiotherapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with HNSCC in usual health care setting. Methods: This was an open-label, single arm study, with retrospective analysis of results. Patients above 18 years of age, and having histologically confirmed, advanced HNSCC were included in the study. The patients were treated with 3 cycles of induction chemotherapy consisting of modified TPF regimen along with nimotuzumab (200 mg IV) on Day 1, followed by radiotherapy for a dose of 66 Gy along with concurrent weekly cisplatin (30 mg/m2) and nimotuzumab (200 mg) throughout the course of radiation. Patients were evaluated using RECIST criteria, 4 weeks after the last cycle of chemotherapy. Results: Sixteen patients were included in this study, with mean age of 54 ± 11 years. Most common sub-site of cancer was oral cavity in 69% (n = 11), followed by pharynx in 19% (n = 3). Four patients had metastasis at the time of presentation. Six patients (37.5%) had progressive disease and four patients (25%) were lost to follow-up. The combination chemotherapy with nimotuzumab was well tolerated. Addition of nimotuzumab to TPF regimen was not associated with added toxicity. Conclusion: Addition of anti-EGFR monocloncal antibody (nimotuzumab) to induction chemotherapy and chemoradiation may be a promising alternative to concurrent chemoradiotherapy in HNSCC due to known over expression of EGFR receptors. The results of this study need further evaluation in a larger study setting.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Subramanium, S. , Balasundaram, V. , Nithya, S. and Kiran, P. (2015) Nimotuzumab with Induction Chemotherapy and Chemo-Radiation in Patients with Advanced Head and Neck Cancer. Journal of Cancer Therapy, 6, 146-152. doi: 10.4236/jct.2015.62016.

References

[1] Reuter, C.W., Morgan, M.A. and Eckardt, A. (2007) Targeting EGF-Receptor-Signalling in Squamous Cell Carcinomas of the Head and Neck. British Journal of Cancer, 96, 408-416.
[2] Trivedi, N.P., Kekatpure, V.D., Trivedi, N.N. and Kuriakose, M.A. (2012) Head and Neck Cancer in India: Need to Formulate Uniform National Treatment Guideline? Indian Journal of Cancer, 49, 6-10. http://dx.doi.org/10.4103/0019-509X.98907
[3] Million, R.R. (1992) Cancer of the Head and Neck. In: De Vita Jr., V.T., Hellman, S. and Rosenberg, S.A., Eds., Cancer: Principles and Practice of Oncology, 4th Edition, JB Lippincott, Philadelphia, 96-420.
[4] Barnes, et al. Head and Neck: Squamous Cell Carcinoma: An Overview. Atlas of Genetics and Cytogenetics in Oncology and Haematology.
http://atlasgeneticsoncology.org/Tumors/HeadNeckSCCID5090.html
[5] Zorat, P.L. and Paccagnella, A. (2004) Randomized Phase III Trial of Neoadjuvant Chemotherapy in Head and Neck Cancer: 10-Year Follow-Up. Journal of the National Cancer Institute, 96, 1714-1717.
[6] Lorch, J.H., Goloubeva, O., Haddad, R.I., et al. (2011) Induction Chemotherapy with Cisplatin and Fluorouracil Alone or in Combination with Docetaxel in Locally Advanced Squamous-Cell Cancer of the Head and Neck: Long-Term Results of the TAX 324 Randomised Phase 3 Trial. The Lancet Oncology, 12, 153-159. http://dx.doi.org/10.1016/S1470-2045(10)70279-5
[7] Vermorken, J.B., Remenar, E., Herpen, C.V., et al. (2007) Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer. The New England Journal of Medicine, 357, 1695-1704. http://dx.doi.org/10.1056/NEJMoa071028
[8] Lorch, J.H., Posner, M.R., Wirth, L.J. and Haddad, R.I. (2008) Induction Chemotherapy in Locally Advanced Head and Neck Cancer: A New Standard of Care? Hematology/Oncology Clinics of North America, 22, 1155-1163. http://dx.doi.org/10.1016/j.hoc.2008.08.004
[9] Posner, M.R., Hershock, D.M., Blajman, C.R., et al. (2007) Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer. The New England Journal of Medicine, 357, 1705-1715. http://dx.doi.org/10.1056/NEJMoa070956
[10] Pointreau, Y., Garaud, P., Chapet, S., et al. (2009) Randomized Trial of Induction Chemotherapy with Cisplatin and 5-Fluorouracil with or without Docetaxel for Larynx Preservation. Journal of the National Cancer Institute, 101, 498-506. http://dx.doi.org/10.1093/jnci/djp007
[11] Jessica, B., Corey, L., Harry, Q., et al. (2013) Induction Chemotherapy with Cetuximab, Carboplatin and Paclitaxel for the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck. Experimental and Therapeutic Medicine, 5, 1247-1253.
[12] Ling, Y., Chen, J., Tao, M., et al. (2012) A Pilot Study of Nimotuzumab Combined with Cisplatin and 5-FU in Patients with Advanced Esophageal Squamous Cell Carcinoma. Journal of Thoracic Disease, 4, 58-62.
[13] Kies, M.S., Holsinger, F.C., Lee, J.J., et al. (2010) Induction Chemotherapy and Cetuximab for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Results from a Phase II Prospective Trial. Journal of Clinical Oncology, 28, 8-14. http://dx.doi.org/10.1200/JCO.2009.23.0425
[14] Babu, K.G., Viswanath, L., et al. (2010) 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. Journal of Clinical Oncology, 28, 15s, Abstr 5530.
[15] Bianco, C., Tortora, G., et al. (2002) Enhancement of Antitumor Activity of Ionizing Radiation by Combined Treatment with the Selective Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor ZD1839 (Iressa). Clinical Cancer Research, 8, 3250-3258.
[16] Rodríguez, M.O., Rivero, T.C., et al. (2010) Nimotuzumab Plus Radiotherapy for Unresectable Squamous-Cell Carcinoma of the Head and Neck. Cancer Biology & Therapy, 9, 343-349.
[17] Wang, H.Q., Quan, T., et al. (2003) Epidermal Growth Factor Receptor-Dependent, NF-kappa B-Independent Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Inhibits Ultraviolet irradiation-Induced Caspases-3, -8, and -9 in Human Keratinocytes. The Journal of Biological Chemistry, 278, 45737-45745.
[18] Li, H.F., Kim, J.S. and Waldman, T. (2009) Radiation-Induced Akt Activation Modulates Radioresistance in Human Glioblastoma Cells. Radiation Oncology, 4, 43.
[19] Nagane, M., Levitzki, A., Gazit, A., Cavenee, W.K. and Huang, H.J. (1998) Drug Resistance of Human Glioblastoma Cells Conferred by a Tumor-Specific Mutant Epidermal Growth Factor Receptor through Modulation of Bcl-XL and Caspase-3-Like Proteases. Proceedings of the National Academy of Sciences of the United States of America, 95, 5724-5729.
[20] Lefebvre, J., Pointreau, Y., Rolland, F., et al. (2011) Sequential Chemoradiotherapy (SCRT) for Larynx Preservation (LP): Results of the Randomized Phase II TREMPLIN Study. Journal of Clinical Oncology, 29, Abstr 5501.
[21] Mesia, R.S., Vazquez, J.J., Grau, J.A., et al. (2009) A Single-Arm Phase II Trial to Evaluate the Combination of Cetuximab Plus Docetaxel, Cisplatin, and 5-Fluorouracil (TPF) as Induction Chemotherapy (IC) in Patients (pts) with Unresectable SCCHN. Journal of Clinical Oncology, 27, 15s, Abstr 6015.
[22] Jain, P., Kumar, P., Pai, V.R. and Parikh, P.M. (2008) Neoadjuvant Chemotherapy or Chemoradio- therapy in Head and Neck Cancer. Indian Journal of Cancer, 45, 83-89.
http://dx.doi.org/10.4103/0019-509X.44061
[23] Zhao, X.Y., Guo, Y., Zhu, Y.X., et al. (2012) Clinical Analysis of Nimotuzumab Plus Cisplatin and Fluorouracil Regimen as Induction Treatment in Resectable Head and Neck Squamous Cell Carcinoma. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 47, 536-539.
[24] Verduzco-Rodríguez, L., Aguirre-González, E.H. and Verduzco-Aguirre, C. (2011) Durable Complete Response Induced by Paclitaxel-Nimotuzumab-Methotrexate Chemotherapy in a Patient with Metastatic Head and Neck Squamous Cell Carcinoma. Hematology/Oncology and Stem Cell Therapy, 4, 182-184.
[25] Wang. X.T., McCullough, K.D., Franke, T.F. and Holbrook, N.J. (2000) Epidermal Growth Factor Receptor-Dependent Akt Activation by Oxidative Stress Enhances Cell Survival. The Journal of Biological Chemistry, 275, 14624-14631.
[26] Rojo, F., Gracias, E., et al. (2010) Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study. Clinical Cancer Research, 16, 2474-2482.
[27] Garrido, G., Tikhomirov, I.A., et al. (2011) Bivalent Binding by Intermediate Affinity of Nimotuzumab: A Contribution to Explain Antibody Clinical Profile. Cancer Biology & Therapy, 11, 373-382.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.