Correspondence

Severe Ocular Irritation and Corneal Deposits Associated with Capecitabine Use

N Engl J Med 2000; 343:740-741September 7, 2000DOI: 10.1056/NEJM200009073431015

Article

To the Editor:

Capecitabine (Xeloda, Roche Laboratories) is an orally administered fluoropyrimidine carbamate used for the treatment of metastatic breast cancer and colon cancer.1-4 We describe two patients in whom marked ocular irritation, decreased vision, and corneal deposits developed during chemotherapy with capecitabine.

Patient 1 was a 48-year-old woman with metastatic breast cancer, a history of keratoconjunctivitis sicca, and 20/20 visual acuity in each eye who had severe bilateral irritation and decreased vision after two cycles of capecitabine (4600 mg per day for 14 days and 3000 mg per day for 14 days). Her visual acuity decreased to 20/40 in the right eye and 20/30 in the left eye, with superficial punctate keratitis and multiple white, granular subepithelial corneal deposits in both eyes (Figure 1Figure 1Slit-Lamp Photographs of Corneal Deposits in Patient 1.). The drug was discontinued for four weeks, with corneal clearing and a return of normal vision in both eyes. The patient agreed to a rechallenge, which resulted in the recurrence of the clinical findings and corneal deposits. The drug was discontinued, with complete clearing of ocular signs and symptoms six weeks later.

The same signs and symptoms developed after treatment with capecitabine in Patient 2, a 53-year-old, one-eyed woman with metastatic colon cancer, a history of keratoconjunctivitis sicca, and 20/20 vision. She received an initial two cycles of 3500 mg of capecitabine per day for 14 days followed by two cycles of 3000 mg per day for 14 days. Her visual acuity decreased to 20/40, with severe ocular irritation, superficial punctate keratitis, and multiple white, granular subepithelial corneal deposits. Capecitabine was discontinued because of the lack of a tumor response, and within two months, the ocular symptoms and corneal deposits had resolved. Neither patient was receiving other chemotherapeutic agents or drugs associated with corneal disorders.

Capecitabine is metabolized in a three-step process to the active agent, 5-fluorouracil, a known ocular irritant.1,5 Although ocular irritation has been reported in 10 percent of patients receiving capecitabine,1 to our knowledge, these are the first reported cases of severe ocular irritation and reversible corneal deposits associated with capecitabine treatment. This association seems probable, since the clinical findings were exactly the same in the two patients, with a positive result on rechallenge in Patient 1 and the resolution of signs and symptoms when the drug was withdrawn in Patient 2.

The ocular toxicity of systemic fluorouracil has been widely reported, but the reported toxicity rarely includes severe ocular irritation and does not include corneal deposits.5 Both of our patients were visually incapacitated and requested the cessation of treatment. Patients receiving higher doses of capecitabine or those with ocular sicca may be at higher risk than other patients. An ophthalmic examination may be indicated for patients with severe ocular symptoms or decreased vision.

Bandana Walkhom, M.D.
F.T. Fraunfelder, M.D.
Casey Eye Institute, Portland, OR 97201

William David Henner, M.D.
Oregon Health Sciences University, Portland, OR 97201

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Citing Articles (8)

Citing Articles

1. 1

   Ribhi Hazin, Jamil Y Abuzetun, Yassine J Daoud, Maysa M Abu-Khalaf. (2009) Ocular complications of cancer therapy: a primer for the ophthalmologist treating cancer patients. Current Opinion in Ophthalmology 20:4, 308-317
   

2. 2

   MILAN MILOVANCEV, CHAD W. SCHMIEDT, ELLISON BENTLEY, MICHELLE SCHWAB, RICHARD R. DUBIELZIG, ANNETTE P. GENDRON-FITZPATRICK, JONATHAN F. McANULTY. (2007) Use of Capecitabine to Prevent Acute Renal Allograft Rejection in Dog Erythrocyte Antigen-Mismatched Mongrel Dogs. Veterinary Surgery 36:1, 10-20
   

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   Katharina E. Schmid, Gabriela V. Kornek, Werner Scheithauer, Susanne Binder. (2006) Update on Ocular Complications of Systemic Cancer Chemotherapy. Survey of Ophthalmology 51:1, 19-40
   

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   K. E. Schmid, S. Binder. (2005) Chemotherapeutische Nebenwirkungen im Augenbereich. Spektrum der Augenheilkunde 19:4, 210-220
   

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   Chris H Takimoto. (2001) The clinical pharmacology of the oral fluoropyrimidines. Current Problems in Cancer 25:3, 134-213
   

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   Jane K. McGavin, Karen L. Goa. (2001) Capecitabine. Drugs 61:15, 2309-2326
   

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   (2001) Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 10:1, 69-84
   

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   &NA;. (2000) Capecitabine. Reactions Weekly &NA;:819, 5-6