title: Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Interventional case series.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Section of Ophthalmology, Department of Head and Neck Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Debraj
authors.initials: D
authors.lastname: Shome
authors.forename: Jonathan
authors.initials: J
authors.lastname: Trent
authors.forename: Ladan
authors.initials: L
authors.lastname: Espandar
authors.forename: Elham
authors.initials: E
authors.lastname: Hatef
authors.forename: Dejka M
authors.initials: DM
authors.lastname: Araujo
authors.forename: C Diane
authors.initials: CD
authors.lastname: Song
authors.forename: Stella K
authors.initials: SK
authors.lastname: Kim
authors.forename: Bita
authors.initials: B
authors.lastname: Esmaeli
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001549:Benzamides; D003320:Corneal Ulcer / Q000139:chemically induced* / Q000188:drug therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D000068877:Imatinib Mesylate; D007414:Intestinal Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011239:Prednisolone / Q000031:analogs & derivatives / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D001549:Benzamides; D005938:Glucocorticoids; D010879:Piperazines; D011743:Pyrimidines; D010767:Phosphorylcholine; C105905:perifosine; D000068877:Imatinib Mesylate; C009935:prednisolone acetate; D011239:Prednisolone; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt