GET THE APP
The Role of Bevacizumab in the Management of Head and Neck Squamo
Chemotherapy: Open Access

Chemotherapy: Open Access
Open Access

ISSN: 2167-7700

+44 1223 790975

Commentary - (2015) Volume 4, Issue 3

View PDF Download PDF

The Role of Bevacizumab in the Management of Head and Neck Squamous Cell Carcinoma Patients

Yuh Baba1* and Yasumasa Kato2
1Department of General Clinical Medicine, Ohu University School of Dentistry, 31-1 Mitsumido, Tomiya-machi, Koriyama City, Fukushima 963-8611, Japan
2Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, 31-1 Mitsumido, Tomiya-machi, Koriyama City, Fukushima 963-8611, Japan
*Corresponding Author: Yuh Baba, Associate Professor of Department of General Clinical Medicine, Ohu University School of Dentistry, 31-1 Mitsumido, Tomiyamachi, Koriyama City, Fukushima 963-8611, Japan, Tel: +81-24-932-9360 Email:

Abstract

Angiogenesis is a crucial step in tumor growth and metastasis. Clinical association of tumor vascularity with tumor aggressiveness has been clearly demonstrated in a wide variety of tumor types including head and neck squamous cell carcinoma (HNSCC) [1]. Thus, determination of microvessel density in tumor tissue can be useful in estimation of prognosis. Inhibition of angiogenesis can repress the growth rate of tumor cells, and also induce apoptosis due to reduced nutrition and oxygen supply to the tumors. Vascular endothelial growth factor (VEGF), which is a major element for many angiogenic processes, binds VEGF receptor (VEGFR) to stimulate endothelial cell proliferation and migration [2,3]. Thus, determination of microvessel density in tumor tissue can be useful as a predictive factor for the effectiveness of bevacizumab in chemoradiotherapeutic strategies.

Keywords: Chemoradiotherapy,tumors,neck squamous cell carcinoma

Introduction

Angiogenesis is a crucial step in tumor growth and metastasis. Clinical association of tumor vascularity with tumor aggressiveness has been clearly demonstrated in a wide variety of tumor types including head and neck squamous cell carcinoma (HNSCC) [1]. Thus, determination of microvessel density in tumor tissue can be useful in estimation of prognosis. Inhibition of angiogenesis can repress the growth rate of tumor cells, and also induce apoptosis due to reduced nutrition and oxygen supply to the tumors. Vascular endothelial growth factor (VEGF), which is a major element for many angiogenic processes, binds VEGF receptor (VEGFR) to stimulate endothelial cell proliferation and migration [2,3]. Thus, determination of microvessel density in tum or tissue can be useful as a predictive factor for the effectiveness of bevacizumab in chemoradiotherapeutic strategies.

The Role of Bevacizumab in Treatment by Chemoradiotherapy in HNSCC

The humanized monoclonal antibody bevacizumab binds VEGF preventing VEGF from binding to VEGFR; as a result, bevacizumab exhibits an antitumor effect. Although bevacizumab alone has only a modest anti-tumor effect, various studies have reported the efficacy of combination bevacizumab and chemoradiotherapy [4,5].

The Role of Bevacizumab in Treatment for Radiation Necrosis in HNSCC

Radionecrosis is a major complication of radiotherapy. Although its incidence is small at approximately 1% [6,7]. It is predicted to increase with increasing use of concomitant chemoradiotherapy. The clinical manifestation of radionecrosis of HNSCC patients, includes hoarseness of voice, difficulty with oral intake, pharyngeal pain, dyspnea owing to mucosal edema, skin fistula, and more. Recently, one possible mechanism of its pathogenesis is thought to be the role of VEGF. Although classically characterized as an angiogenic factor, VEGF also potentiates capillary permeability [8]. Nonoguchi et al. showed overexpression of VEGF in resected radiation necrosis lesions [9]. Furthermore, degree of radiation injury has been correlated with amount of VEGF expression [10]. Moreover, Levin et al. indicated that bevacizumab is a treatment option in patients who suffer from radiation necrosis secondary to treatment of head, neck and brain cancers [11]. We previously reported a case of a 67-year-old Japanese man who presented with a condition extremely difficult to diagnose differentially as radionecrosis or tumor recurrence after chemoradiotherapy for hypopharyngeal cancer [12]. Although tumor recurrence was suspected from clinical conditions and computed tomography findings, pathological analysis revealed no evidence of tumor recurrence, and successful therapy with steroids and antibiotics reduced the mucosa edema. Bevacizumab may be considered a treatment option of radiation necrosis in cases of unsuccessful therapy with steroids and antibiotics, and appropriate medical imaging studies, including MRI and PET scans are not helpful in excluding tumor recurrence.

References

  1. Sauter ER, Nesbit M, Watson JC, Klein-Szanto A, Litwin S, et al. (1999) Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck.Clin Cancer Res5: 775-782.
  2. Takahashi T, Ueno H, Shibuya M (1999) VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells.Oncogene18:2221-2230.
  3. Rousseau S, Houle F, Landry J, Huot J (1997) p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells.Oncogene15:2169-2177.
  4. Fury MG, Xiao H, Sherman EJ, Baxi S, Smith-Marrone S, et al. (2015) Phase II trial of bevacizumab + cetuximab + cisplatin with concurrent intensity-modulated radiation therapy for patients with stage III/IVB head and neck squamous cell carcinoma.
  5. Yao M, Galanopoulos N, Lavertu P, Fu P, Gibson M, et al. (2014) Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell carcinoma of the head and neck.Head Neck.
  6. Oppenheimer RW, Krespi YP, Einhorn RK (1989) Management of laryngealradionecrosis: animal and clinical experience. Head Neck 11: 252-256.
  7. Stell PM, Morrison MD (1973) Radiation necrosis of the larynx. Etiology and management. Arch Otolaryngol98: 111-113.
  8. Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, et al. (1989) Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.J Clin Invest84:1470-1478.
  9. Nonoguchi N, Miyatake S, Fukumoto M, Furuse M, Hiramatsu R, et al. (2011) The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles.J Neurooncol105: 423-431.
  10. Kim JH, Chung YG, Kim CY, Kim HK, Lee HK (2004) Upregulation of VEGF and FGF2 in normal rat brain after experimental intraoperative radiation therapy.J Korean Med Sci19: 879-886.
  11. Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, et al. (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system.Int J RadiatOncolBiolPhys79: 1487-1495.
  12. Baba Y, Kato Y, Ogawa K (2011) Unusual computed tomography findings of radionecrosis after chemoradiation of stage IV hypopharyngeal cancer: a case report.Journal of Medical Case Reports 5: 25.
Citation: Baba Y, Yasumasa K (2015) The Role of Bevacizumab in the Management of Head and Neck Squamous Cell Carcinoma Patients.Chemo Open Access 4:163.

Copyright: © 2015 Baba Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Top