Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine.

Published

Journal Article

PURPOSE: Perifosine is a novel alkylphospholipid with antiproliferative properties attributed to protein kinase B inhibition. The authors describe a form of ulcerative keratitis in 5 patients with advanced gastrointestinal stromal tumor (GIST) enrolled in a phase I/II trial of perifosine in combination with imatinib. DESIGN: Interventional case series. PARTICIPANTS: Five patients (1 man, 4 women) with imatinib-resistant metastatic GIST who received a combination of imatinib and perifosine orally. METHODS: The medical records were reviewed retrospectively. MAIN OUTCOME MEASURES: Ocular toxicity and ulcerative keratitis associated with perifosine. RESULTS: The ocular symptoms included redness, irritation, tearing, photophobia, and a gradual decrease in vision. Slit-lamp biomicroscopy in each case revealed a peripheral, paralimbal, ring-shaped, superficial corneal stromal infiltration and ulcerative keratitis, reminiscent of the autoimmune keratitis in conditions such as rheumatoid arthritis. The ulcerative keratitis was unilateral in 3 and bilateral in 2 patients; it was National Cancer Institute grade II (symptoms interfering with function but not interfering with activities of daily living) in all patients. All 5 patients had imatinib-resistant metastatic GIST and had continued on the highest dose of imatinib tolerated and initiated therapy with perifosine 100 mg daily or 900 mg weekly. A combination of topical steroids, topical antibiotics, and lubricating drops were used to manage ulcerative keratitis. In the first 3 patients, ulcerative keratitis initially was treated with topical antibiotics without improvement, but subsequently they improved significantly after topical steroids were added. CONCLUSIONS: A vision-threatening form of ulcerative keratitis may occur in patients taking perifosine. It is possible that imatinib in combination with perifosine contributes to this corneal toxicity; however, the authors are unaware of this ocular toxicity having been reported for imatinib when used without perifosine. The visual loss associated with perifosine may be reversible if detected and treated early and with judicious early use of topical steroids, topical antibiotic coverage, and lubrication.

Full Text

Duke Authors

Cited Authors

  • Shome, D; Trent, J; Espandar, L; Hatef, E; Araujo, DM; Song, CD; Kim, SK; Esmaeli, B

Published Date

  • March 2008

Published In

Volume / Issue

  • 115 / 3

Start / End Page

  • 483 - 487

PubMed ID

  • 18201764

Pubmed Central ID

  • 18201764

Electronic International Standard Serial Number (EISSN)

  • 1549-4713

Digital Object Identifier (DOI)

  • 10.1016/j.ophtha.2007.11.016

Language

  • eng

Conference Location

  • United States