Histopathologic Evidence of Capecitabine Corneal Toxicity in Dogs

Abstract

In an experimental model of transplant rejection, renal transplants were performed on 6 mixed-breed dogs. Capecitabine (CPC) was administered as an oral immunosuppressive agent. All recipients received systemic CPC, cyclosporine (CSA), prednisolone, and famotidine throughout the study. Two dogs developed superficial keratitis, which was characterized by multifocal geographic erosions, superficial corneal epithelial pigmentation, and corneal neovascularization. These clinical signs correlated with the dose of CPC given, whereas other drug doses remained unchanged. After euthanasia, routine histologic sections were stained with hematoxylin and eosin and with alcian blue periodic acid-Schiff for light microscopic evaluation. Ocular histopathologic abnormalities were limited to neovascularization and inflammatory infiltrate of the anterior corneal stroma and abnormal basal cell morphology, disorganization, thinning, and pigmentation of the corneal epithelium. The purpose of this communication is to describe the clinical and histopathologic evidence of CPC corneal toxicity in dogs.

Use of oral paclitaxel for the treatment of bladder tumors in dogs

“…We initiated chemotherapy with capecitabine (Xeloda, F. Hoffmann-LaRoche Ltd., Basel, Switzerland; 500 mg/m 2 PO, q 24 hr) and piroxicam (0.3 mg/kg PO, q 24 hr). After 3 weeks, dysuria was ameliorated; however, we observed corneal perforation consistent with a previous report of capecitabine-associated corneal toxicity[20].…”

The Potential Protective Role of Hesperidin Against Capecitabine-Induced Corneal Toxicity in Adult Male Albino Rat. Light and Electron Microscopic Study

“…This was similar to the results of other researchers who studied the capecitabine induced corneal toxicity in dogs [46] . This epithelial thinning might be due to cellular degeneration and loss of dead cells with subsequent slow rate of cellular proliferation and regeneration [47] .…”

Assessment of plasma uracil-to-dihydrouracil concentration ratio as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency

“…3 Veterinary use of capecitabine has primarily been investigated as an immunosuppressant following renal transplantation in dogs. [4][5][6] In those studies, [4][5][6] capecitabine was effective in preventing rejection of renal allografts in dog erythrocyte antigenmismatched mongrel dogs, but fatal, irreversible neurotoxicosis, which was potentially attributed to the drug, developed in 2 of 8 allograft recipients. This unacceptable severity of toxic effects has prohibited further clinical investigation.…”

“…This unacceptable severity of toxic effects has prohibited further clinical investigation. [4][5][6] Because the maximally tolerated dosages of these drugs are unknown, it is plausible that some of the reported toxic effects may be alleviated with optimized, species-specific dosing regimens. However, the toxic effects may also be related to insufficient activity of DPD, the rate-limiting enzyme in metabolism of 5-FU.…”