Persisting Corneal Erosion Under Cetuximab (Erbitux) Treatment (Epidermal Growth Factor Receptor Antibody)

Foerster, Claudia; Cursiefen, Claus; Kruse, Friedrich E.

doi:10.1097/ico.0b013e318166f483

Cited by 65 publications

(44 citation statements)

References 6 publications

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“…38 There is multiple-layer distribution of active AKT in the normal corneal epithelium from 2 dpw to 23 dpw, while there is only basal distribution in the diabetic, suggesting that p-AKT may play a role in cell proliferation, differentiation, and even cell junction formation after injury. Echoing our findings are the observations that inhibiting EGFR function with cetuximab and gefitinib for cancer treatments resulted in ocular abnormalities in patients, including diffuse punctate keratitis and corneal erosion [53][54][55][56] and that ulcerative keratitis occurs in gastrointestinal cancer patients taking perifosine, an AKT inhibitor. 57 While the effects of hyperglycemia on wound healing apparatus, such as cytoskeleton and integrin-mediated cell adhesion, remain undetermined, this study, along with our recent publications, 38 indicates that the impaired or blunted EGFR signaling response to injury is a major cause for delayed epithelial wound healing seen in diabetic rat and human corneas.…”

Section: Discussionmentioning

confidence: 69%

Corneal Complications in Streptozocin-Induced Type I Diabetic Rats

Yin¹,

Huang²,

Chen³

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study seeks to characterize corneal functions and complications in a streptozocin (STZ)-induced rat model of type I diabetes mellitus (DM) and to understand the pathogenesis of diabetic keratopathy. METHODS. DM was induced via STZ injection in Sprague-Dawley rats. Body weight, length, and corneal size were measured and compared with the age-matched normal controls. Corneal morphology and histology were evaluated with slit lamp, digital confocal microscopy and hematoxylin and eosin staining. Tear secretion was measured with cotton threads, and corneal sensitivity was determined with an esthesiometer. Protein expression and distribution were assessed with Western blotting and immunohistochemistry. Wound healing was determined using an in vivo corneal epithelial debridement model. RESULTS. Compared with the normal control rats, STZ rats had reduced body weight, and body length, but minimally affected corneal size. No significant changes in ocular surface regularity, corneal thickness, and morphology were noted in diabetic corneas. STZ rats showed stronger Rose Bengal staining, decreased tear secretion, slightly attenuated sensitivity, less innervation, delayed epithelial wound healing, and impaired epidermal growth factor receptor signaling in their corneas. While the expression of adherens junction protein β-catenin, and tight junction proteins occludin and ZO-1 was unchanged, the formation of these junctions after wound closure was delayed. CONCLUSIONS. Pathogenesis of diabetic keratopathy involves multiple tissues and/or cell types and several events including reduced tear secretion, impaired innervation, weakened cell junction, and altered wound responses. These insights may prove useful for the clinical translation of evolving strategies for the management and treatment of diabetic corneal complications.

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Section: Discussionmentioning

confidence: 69%

Corneal Complications in Streptozocin-Induced Type I Diabetic Rats

Yin¹,

Huang²,

Chen³

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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“…Ocular surface toxicity with these medications seems to be infrequent but has been reported in association with cetuximab, erlotinib, and gefitinib. Blepharitis, 17,18 conjunctivitis, 17,18 and corneal erosions 19 have been reported in association with cetuximab therapy. In 1 patient with persistent corneal erosions attributed to cetuximab, treatment with human EGF improved the healing of persistent corneal epithelial defects.…”

Section: Case Reportmentioning

confidence: 98%

“…In 1 patient with persistent corneal erosions attributed to cetuximab, treatment with human EGF improved the healing of persistent corneal epithelial defects. 19 It is also interesting to note that in phase I and phase II trials of gefitinib, the most clinically significant ophthalmologic side effects observed were reversible corneal erosions that occurred at doses greater than the currently recommended dose of gefitinib (250 mg/d). 20 However, studies in a rat model of corneal epithelial injury have demonstrated a dose-dependent impairment of corneal epithelial wound healing at doses exceeding those used for patients (40-80 mg/kg/d).…”

Section: Case Reportmentioning

confidence: 98%

Corneal Verticillata After Dual Anti-Epidermal Growth Factor Receptor and Anti-Vascular Endothelial Growth Factor Receptor 2 Therapy (Vandetanib) for Anaplastic Astrocytoma

Yeh

Fine

Smith

2009

Cornea

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Vandetanib (ZD6474), a protein tyrosine kinase inhibitor with dual anti-EGFR and anti-vascular endothelial growth factor receptor 2 action, may have contributed to the formation of corneal verticillata in our patient. Inhibition of EGFR, which is involved with corneal epithelial cell migration and wound healing, may play a role in the pathogenesis underlying corneal vortex keratopathy and ocular surface conditions with significant epithelial turnover.

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“…[85][86][87] These effects are not surprising given the role of EGFR family members in the cornea healing process. 88,89 The presence of rash as a positive predictor of improved outcome with EGFR inhibitors including cetuximab was suggested initially in studies of cetuximab in HNSCC and colorectal cancer.…”

Section: Tolerabilitymentioning

confidence: 99%

The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer

Tejani

Cohen²,

Mehra

2010

BTT

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Recurrent and/or metastatic squamous cell carcinoma of the head and neck (HNSCC) continues to be a source of significant morbidity and mortality worldwide. Agents that target the epidermal growth factor receptor (EGFR) have demonstrated beneficial effects in this setting. Cetuximab, a monoclonal antibody against the EGFR, improves locoregional control and overall survival when used as a radiation sensitizer in patients with locoregionally advanced HNSCC undergoing definitive radiation therapy with curative intent. Cetuximab is also active as monotherapy in patients whose cancer has progressed on platinum-containing therapy. In the first-line setting for incurable HNSCC, cetuximab added to platinum-based chemotherapy significantly improves overall survival compared with standard chemotherapy alone. These positive results have had a significant impact on the standard of care for advanced HNSCC. In this review, we will discuss the mechanism of action, clinical data and common toxicities that pertain to the use of cetuximab in the treatment of advanced incurable HNSCC.

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Persisting Corneal Erosion Under Cetuximab (Erbitux) Treatment (Epidermal Growth Factor Receptor Antibody)

Abstract: Cetuximab (Erbitux) can cause impairment of corneal wound healing as an ocular side effect. Patients concerned may benefit from application of EGF eyedrops.

Cited by 65 publications

References 6 publications

Corneal Complications in Streptozocin-Induced Type I Diabetic Rats

Corneal Complications in Streptozocin-Induced Type I Diabetic Rats

Corneal Verticillata After Dual Anti-Epidermal Growth Factor Receptor and Anti-Vascular Endothelial Growth Factor Receptor 2 Therapy (Vandetanib) for Anaplastic Astrocytoma

The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer

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