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 Table of Contents  
Year : 2017  |  Volume : 6  |  Issue : 3  |  Page : 190-191

Intralesional bevacizumab (Avastin®) as a novel addition to infantile hemangioma management: A medical hypothesis

1 Cancer Research Center, Semnan University of Medical Sciences, Semnan; Department of Ophthalmology, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Orthodontics, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Web Publication21-Sep-2017

Correspondence Address:
Bahareh Abtahi-Naeini
Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrpp.JRPP_17_38

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How to cite this article:
Pourazizi M, Kabiri S, Abtahi-Naeini B. Intralesional bevacizumab (Avastin®) as a novel addition to infantile hemangioma management: A medical hypothesis. J Res Pharm Pract 2017;6:190-1

How to cite this URL:
Pourazizi M, Kabiri S, Abtahi-Naeini B. Intralesional bevacizumab (Avastin®) as a novel addition to infantile hemangioma management: A medical hypothesis. J Res Pharm Pract [serial online] 2017 [cited 2020 Jul 14];6:190-1. Available from: http://www.jrpp.net/text.asp?2017/6/3/190/215235

Dear Editor,

Infantile hemangiomas (IHs) are benign tumors of the vascular endothelium. There are numerous medications available for the treatment of IH, including wait-and-see policy, laser therapy, systemic and local medications, sclerotherapy, radiotherapy, and surgery. To obtain the best treatment outcomes, the treatment protocol should be individualized and comprehensive as well as sequential.[1],[2]

Studies have confirmed the importance of vascular endothelial growth factor (VEGF) pathway in IH and the fact that it is a major stimulus responsible for cell proliferation and angiogenesis.[3]

Some of the medications are developed to directly modulate vascular proliferation. Although data on the efficacy of local pharmacotherapy in IH are limited, the administration of local medication is often preferred.

Intralesional injection of some medications including corticosteroids can be considered as an effective adjuvant treatment for involution phase of IH in patients with poor response to oral drug therapy. The advantages of intralesional injection include short course, reduced financial cost, good tolerance, and minimal major complications.[2]

This may lead to contraindications and development of adverse effects of administrated systemic medications in small or superficial IH.[1],[4],[5]

Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting VEGF-A.[6] Originally, Bevacizumab (Avastin ®, Genentech Inc., San Francisco, CA, USA) was approved by the US Food and Drug Administration (FDA) for certain metastatic cancers including lung, breast, renal, and brain as a systemic administration.[6]

In addition, the FDA approval of bevacizumab intravitreal injections on vitreous cavities has been performed without significant intraocular toxicity in proliferative diabetic retinopathy (PDR).[7] Intravitreal Avastin ® inhibits the locally increased levels of VEGF in the vitreous cavity in patients with PDR and induces a short-term regression of new vessels in vasoproliferative diseases.[8],[9]

In addition, the current evidence indicates that injection of intravitreal bevacizumab is an effective for achieving regression of acute retinopathy of prematurity in a newborn with distinct ocular advantages.[10]

Therefore, Avastin ® has local anti-VEGF effects.

Jeng et al. reported effective treatment of malignant transformation of IH to angiosarcoma with systemic chemotherapy and Avastin ®.[11] Avastin ® is an anti-angiogenic agent drug capable of suppressing the pro-angiogenic signaling pathway, following activating mutations in the RAS gene. This gain of function mutation promotes angiogenesis. Since this pathway begins extracellularly with VEGF binding its receptor VEGFR, anti-VEGF is used for the treatment of angiosarcoma and Kaposi sarcoma.[11]

Halin et al. in 2008 described an experimental model of the topical application of VEGF receptor tyrosine-kinase inhibitors (NVP-BAW2881) in reduced inflammatory responses elicited in pig skin by ultraviolet B irradiation.[12] Their results demonstrate that a decreased local VEGF may be due to the local application of NVP-BAW2881.[12]

Taken together, considering the important role of VEGF involved in the pathophysiology of IH and the anti-angiogenesis effect of Avastin ®, we hypothesized that Avastin ® is a useful addition to the limited local anti-IH ammunition. This was consistent with the study by Steeples et al. in 2013, who described the intralesional application of anti-VEGF in the treatment of palpebral pyogenic granuloma associated with pregnancy in a case report.[13]

The importance of our letter is to introduce a potentially promising medication for a common but sometimes debilitating disease during infancy and can encourage clinical researchers, especially those who have access to this drug, to conduct further trials on this topic.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Asilian A, Mokhtari F, Kamali AS, Abtahi-Naeini B, Nilforoushzadeh MA, Mostafaie S. Pulsed dye laser and topical timolol gel versus pulse dye laser in treatment of infantile hemangioma: A double-blind randomized controlled trial. Adv Biomed Res 2015;4:257.  Back to cited text no. 1
[PUBMED]  [Full text]  
Zheng JW, Zhang L, Zhou Q, Mai HM, Wang YA, Fan XD, et al. Apractical guide to treatment of infantile hemangiomas of the head and neck. Int J Clin Exp Med 2013;6:851-60.  Back to cited text no. 2
Chang J, Most D, Bresnick S, Mehrara B, Steinbrech DS, Reinisch J, et al. Proliferative hemangiomas: Analysis of cytokine gene expression and angiogenesis. Plast Reconstr Surg 1999;103:1-9.  Back to cited text no. 3
Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol 2010;128:255-6.  Back to cited text no. 4
McCuaig CC, Dubois J, Powell J, Belleville C, David M, Rousseau E, et al. Aphase II, open-label study of the efficacy and safety of imiquimod in the treatment of superficial and mixed infantile hemangioma. Pediatr Dermatol 2009;26:203-12.  Back to cited text no. 5
Shih T, Lindley C. Bevacizumab: An angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 2006;28:1779-802.  Back to cited text no. 6
Arevalo JF, Fromow-Guerra J, Sanchez JG, Maia M, Berrocal MH, Wu L, et al. Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degeneration: Results of the Pan-American Collaborative Retina Study Group at 12 months follow-up. Retina 2008;28:1387-94.  Back to cited text no. 7
Simunovic MP, Maberley DA. Anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy: A systematic review and meta-analysis. Retina 2015;35:1931-42.  Back to cited text no. 8
Minnella AM, Savastano CM, Ziccardi L, Scupola A, Falsini B, Balestrazzi E. Intravitreal bevacizumab (Avastin) in proliferative diabetic retinopathy. Acta Ophthalmol 2008;86:683-7.  Back to cited text no. 9
VanderVeen DK, Melia M, Yang MB, Hutchinson AK, Wilson LB, Lambert SR. Anti-vascular endothelial growth factor therapy for primary treatment of type 1 retinopathy of prematurity: A report by the American Academy of Ophthalmology. Ophthalmology 2017;124:619-33.  Back to cited text no. 10
Jeng MR, Fuh B, Blatt J, Gupta A, Merrow AC, Hammill A, et al. Malignant transformation of infantile hemangioma to angiosarcoma: Response to chemotherapy with bevacizumab. Pediatr Blood Cancer 2014;61:2115-7.  Back to cited text no. 11
Halin C, Fahrngruber H, Meingassner JG, Bold G, Littlewood-Evans A, Stuetz A, et al. Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Am J Pathol 2008;173:265-77.  Back to cited text no. 12
Steeples LR, Bonshek R, Morgan L. Intralesional bevacizumab for cutaneous capillary haemangioma associated with pregnancy. Clin Exp Ophthalmol 2013;41:413-4.  Back to cited text no. 13


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