Periodontal disease in a patient receiving Bevacizumab: a case report
© Gujral et al; licensee BioMed Central Ltd. 2008
Received: 12 October 2007
Accepted: 13 February 2008
Published: 13 February 2008
Bevacizumab is a monoclonal antibody that inhibits the action of vascular endothelial growth factor (VEGF) thereby acting as an angiogenesis inhibitor. As a result, supply of oxygen and nutrients to tissues is impaired and tumour cell growth is reduced. Reported side effects due to bevacizumab are hypertension and increased risk of bleeding. Bowel perforation has also been reported. Periodontal disease in patients on bevacizumab therapy has not been reported before.
We report a case of a forty-three year old woman who developed periodontitis whilst receiving bevacizumab for lung cancer. The periodontal disease remained stable on discontinuation of the drug.
Further investigations are needed to determine the mechanism for bevacizumab-induced periodontal disease.
Bevacizumab is a monoclonal antibody that inhibits the action of vascular endothelial growth factor (VEGF) thereby acting as an angiogenesis inhibitor and preventing the formation of new blood vessels, including those that surround and supply cancer cells. As a result, supply of oxygen and nutrients to tissues is impaired and tumour cell growth is reduced. Cancerous tumours may become slower growing or even smaller.
It is this property that has found non-oncological uses for bevacizumab as its anti-angiogenesis effect has been useful in the treatment of proliferative (neovascular) eye diseases, particularly age-related macular degeneration [1–4].
Periodontal diseases range from simple gum inflammation to serious disease that results in major damage to the soft tissue and bone that support the teeth. Risk factors for the development of periodontal disease are smoking, hormonal changes in women, poor nutrition resulting in deficiencies in calcium and certain vitamins (especially vitamins B and C), diabetes, gingivitis, stress, immunosuppressive illnesses, genetic susceptibility and certain medications (including chemotherapy drugs and those that reduce the production of saliva such as antidepressants, antihistamines, antiepileptics, and calcium channel blockers). [9, 10].
Previous studies have shown increased levels of VEGF in gingival and gingival crevicular fluid in patients with periodontitis, in keeping with an inflammatory process induced by periodontopathogens, with neovascularisation causing swelling and oedema [11, 12]. It is possible that VEGF levels are high in an attempt to stimulate angiogenesis and facilitate healing. Regeneration of periodontal structures lost during periodontal disease is regulated by, among other things, interactions between cells and growth factors.
A 43 year old lady presented in 2005 with wheeze, shortness of breath and pain in the right back. She had no other symptoms of note and was an ex-smoker. The patient had had an ovarian cystectomy in 2004 which was complicated by fistula formation requiring several laparotomies.
At bronchoscopy, obstruction by a large right middle lobe tumour was noted and biopsy confirmed an adenocarcinoma. Subsequent PET-CT scanning revealed extensive soft tissue abnormalities in the right paravertebral region posteriorly and lymphadenopathy in the subcarinal, contralateral and pretracheal regions. The final staging was T2N3M0 (IIIB).
The patient was enrolled in the AVAiL trial (AVA stin I n L ung cancer – Trial No. BO17704) – a study in which the primary objective is to evaluate safety and efficacy of two doses of bevacizumab in combination with gemcitabine and cisplatin and determine the optimal dose of bevacizumab. The trial is a randomised, double-blind, multicentre, 2-stage, phase III study of bevacizumab and gemcitabine/cisplatin versus placebo and gemcitabine/cisplatin in patients with advanced or recurrent non-small cell lung carcinoma who have not received prior chemotherapy. The patient was randomised to receive gemcitabine/cisplatin and bevacizumab on the maintenance arm.
This case is, to the best of our knowledge, the first reported of a patient developing periodontal disease whilst receiving bevacizumab. Although it would be difficult to exclude all other risk factors in this patient, the onset of periodontal disease on commencement of bevacizumab and the fact that the disease remained stable on discontinuation of the drug points to this as the cause.
In this case, one might expect low plasma levels of VEGF with the use of bevacizumab. It is possible that, as an angiogenesis inhibitor, bevacizumab prevents the formation of new blood vessels, resulting in a lack of supply of oxygen and nutrients to the tissues. This may result in ischaemia and necrosis (consequently inhibiting reversal of the process and impairing wound healing). Further investigations are therefore needed to determine the mechanism for bevacizumab-induced periodontal disease.
Written consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Joeres S, Heussen FM, Treziak T, Bopp S, Joussen AM: Bevacizumab (Avastin) treatment in patients with retinal angiomatous proliferation. Graefes Arch Clin Exp Ophthalmol. April 17 2007,Google Scholar
- Meyerle CB, Freund KB, Iturralde D, Spaide RF, Sorenson JA, Slakter JS, Klancnik JM, Fisher YL, Cooney MJ, Yannuzzi LA: Intravitreal bevacizumab (avastin) for retinal angiomatous proliferation. Retina. 2007, 27 (4): 451-457. 10.1097/IAE.0b013e318030ea80.View ArticlePubMedGoogle Scholar
- Giansanti F, Virgili G, Bini A, Rapizzi E, Giacomelli G, Donati MC, Verdina T, Menchini U: Intravitreal bevacizumab therapy for choroidal neovasculariszation secondary to age-related macular degeneration: 6 month results of an open-label uncontrolled clinical study. Eur J Ophthalmol. 2007, 17 (2): 230-237.PubMedGoogle Scholar
- Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, Sanchez JG, Wu L, Maia M, Berrocal MH, Solis-Vivanco A, Farah ME: Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6 month follow-up. Ophthalmology. 2007, 114 (4): 743-750. 10.1016/j.ophtha.2006.12.028.View ArticlePubMedGoogle Scholar
- Caprioni F, Fornarini G: Bevacizumab in the treatment of metastatic colorectal cancer. Future Oncol. 2007, 3 (2): 131-139. 10.2217/147966126.96.36.199.View ArticleGoogle Scholar
- Saif MW, Elfiky A, Salem RR: Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol. Mar 14 2007,Google Scholar
- Zhu X, Wu S, Dahut WL, Parikh CR: Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis. 2007, 49 (2): e23-29. 10.1053/j.ajkd.2006.11.039.View ArticleGoogle Scholar
- Heinzerling JH, Heurta S: Bowel perforation from bevacizumab for the treatment of metastatic colon carcinoma: incidence, aetiology, and management. Curr Surg. 2006, 63 (5): 334-337. 10.1016/j.cursur.2006.06.002.View ArticlePubMedGoogle Scholar
- Mangini F, Santacroce L, Bottalico L: Periodontitis and systemic disease. Clin Ter. 2006, 157 (6): 541-548.PubMedGoogle Scholar
- Ciancio SG: Medications: a risk factor for periodontal disease diagnosis and treatment. J Periodontol. 2005, 76 (11 suppl): 2085-2088.Google Scholar
- Sakallioglu EE, Aliyev E, Lutfioglu M, Yavuz U, Acikgoz G: Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients. Clin Oral Investig. 2007, 11 (2): 115-120. 10.1007/s00784-006-0097-5.View ArticlePubMedGoogle Scholar
- Guneri P, Unlu F, Yesilbek B, Bayraktar F, Kokuludag A, Hekimgil M, Boyacioglu H: Vascular endothelial growth factor in gingival tissues and crevicular fluids of diabetic and healthy periodontal patients. J Periodontol. 2004, 75 (1): 91-97. 10.1902/jop.2004.75.1.91.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.