Ocular surface adverse events of systemic epidermal growth factor receptor inhibitors (EGFRi): A prospective trial

J Fr Ophtalmol. 2018 Dec;41(10):955-962. doi: 10.1016/j.jfo.2018.07.005. Epub 2018 Nov 23.

Abstract

Purpose: Controversy exists regarding the safety of agents that systemically inhibit epidermal growth factor receptor (EGFRi) in oncologic patients in terms of toxicity to the ocular surface. We performed a prospective clinical study comparing the ocular surface toxicity of systemic EGFRi between a case and a control group.

Methods: Patients with lung or colon cancer were divided in two groups: 25 patients treated with systemic EGFRi and 25 control patients without EGFRi treatment. Patients in both groups were chemotherapy naive. Four visits were scheduled in a one year period comparing signs and symptoms in terms of symptom questionnaires (SIDEQ, OSDI and AVS), corneal fluorescein staining (Oxford test), tear production (Schirmer's test) and a quantitative evaluation of conjunctival chemosis and hyperemia. Basal epithelial cell density (CEBD) and corneal subepithelial nerve fiber density (CNFD) were measured and compared using confocal microscopy (Heidelberg Engineering, Germany). The differences in each variable were compared with the analysis of variance (ANOVA). A P value<0.05 was considered significant for all comparisons.

Results: No statistically significant differences were found between patients under EGFRi treatment and the age-matched controls in the variables analyzed. When cases and controls were evaluated separately, the case group showed a significantly worse progression of signs (chemosis score, CFS, Schirmer's) as well as in terms of CEBD and CNFD (all P<0.05).

Conclusion: Systemic EGFRi may increase dry eye signs as well as decrease CEBD and CNFD. This study may help us to understand the true toxicity of EGFRi to the ocular surface.

Keywords: Chemotherapy; Chimiothérapie; Confocal microscopy; Cornea; Cornée; Effets secondaires sur la surface oculaire; Epidermal growth factor receptor inhibitors; Inhibiteurs du récepteur du facteur de la croissance épidermique; Microscopie confocale; Ocular surface secondary effects.

Publication types

  • Observational Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Case-Control Studies
  • Colorectal Neoplasms / drug therapy
  • Cornea / diagnostic imaging
  • Cornea / drug effects*
  • Cornea / pathology
  • Dry Eye Syndromes / chemically induced*
  • Dry Eye Syndromes / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / immunology
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Lung Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Organoplatinum Compounds / therapeutic use
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*

Substances

  • Antibodies, Monoclonal
  • Organoplatinum Compounds
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol