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Novel ocular toxicity associated with fibroblast growth factor receptor (FGFR) inhibitors in cancer treatment: observational case series
  1. Daniel Velazquez-Villoria1,
  2. Analia Azaro2,
  3. Jordi Rodon3,
  4. Cinta Hierro2,
  5. Danai Kyriakou4,
  6. Jose Garcia-Arumi4,
  7. Miguel Angel Zapata4
  1. 1Department of Ophthalmology, POVISA Hospital, Pontevedra, Spain
  2. 2Medical Oncology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  3. 3Molecular Therapeutics Research Unit, Medical Oncology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
  4. 4Department of Ophthalmology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
  1. Correspondence to Dr Daniel Velazquez-Villoria, Department of Ophthalmology, POVISA hospital, Pontevedra E-36001, Spain; dvvilloria{at}gmail.com

Abstract

Aims To describe novel ocular toxicity in patients with metastatic cancer undergoing chemotherapy with fibroblast growth factor receptor (FGFR) inhibitors.

Methods This observational case series study included five patients with advanced cancer who received selected pan-FGFR inhibitors as single chemotherapy in the framework of a dose-finding study and phase I and phase II clinical studies. In all cases, subfoveal neurosensory retinal detachment was diagnosed. All patients underwent complete ophthalmic examination with swept source optical coherence tomography (SS-OCT) and OCT angiography in selected cases.

Results SS-OCT showed subfoveal neuroretinal detachment soon after treatment induction with FGFR inhibitors. Lesions were asymptomatic with a tendency to persist at follow-up without improvement. Complete resolution of subretinal fluid was only observed in two patients after a two-level dose reduction and after 4 weeks of stopping medication, respectively. In the remaining three patients, subfoveal neuroretinal detachment showed small fluctuations at follow-up visits. Permanent sequelae did not develop and none of the patients was withdrawn from clinical studies because of ocular toxicity. No abnormalities in retinal or choroidal vasculature as well as choroidal thickness were documented.

Conclusions Detailed characteristics of subfoveal neurosensory retinal detachment associated with FGFR inhibitor use for metastatic cancer are reported for the first time. Choroidal vasculature seems uninvolved. Isolated subfoveal lesions and longer persistence of subretinal fluid may be differential features from retinal toxicity associated with mitogen-activated protein kinase inhibitors.

Trial registration number NCT02150967; NCT 01976741; NCT 02052778, Pre-results.

  • retina
  • imaging
  • drugs
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Footnotes

  • Contributors DV-V, CH and DK researched data and wrote and edited the manuscript. AA, JR, JG-A and MAZ analysed the data, contributed to the discussion and reviewed/edited the manuscript. DV-V and MAZ contributed to the study design and discussion, reviewed the manuscript, and are the guarantors of this work and as such had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The Ethics Committee for Clinical Research of Hospital Universitari Vall d’Hebron approved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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