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R.F. Melendez, J.M. Harrison, E.K. Rowinsky, L.A. Hammond, T.D. Fitzsimmons; Acute Retinal Toxicity from a Novel Anti-tumor Agent, MGI-114 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4927.
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Purpose: MGI-114 (Irofulven, Hydroxymethylacylfulvene) is a new anti-tumor agent derived from a mushroom toxin that is currently undergoing investigation in several multi-centered clinical trials for treatment of a variety of solid tumors. We report symptoms and signs of acute retinal toxicity in three patients who received a single, initial dose of MGI-114. Methods: Observational case series. Three patients enrolled in a Phase II clinical trial for metastatic breast carcinoma had ophthalmologic examinations within 14 days of first administration of MGI-114. Patients had complete ocular examinations, and visual function was evaluated by color vision tests, visual field tests, electroretinograms (ERG), and visual evoked potentials (VEP). Results: Within several days of the first dose of MGI-114, patients described severe visual disturbances including photophobia, photopsias, and impaired color vision. Eye examinations were notable for normal visual acuity, clear anterior segments, and unremarkable retinas. Color vision was defective by Ishihara color plate tests. Visual field abnormalities consisted of irregular, dense scotomas and generalized depression. ERG abnormalities common to all patients were reduced, absent and/or prolonged responses arising in the cone system; rod responses were within normal parameters. Pattern and flash VEPs were normal. No patient received additional MGI-114 treatments. Over several weeks, each patient reported modest subjective improvement of visual disturbances, but ERGs remained abnormal at two-month follow-up. Conclusions: The acute onset of visual disturbances, color vision abnormalities, and abnormal electrophysiological data were all consistent with retinal toxicity secondary to MGI-114. No physical signs on standard ocular examinations were apparent, but ERG data indicate widespread cone system pathology affecting the outer and middle retina. The acute onset and the lack of severe, diffuse ERG reduction are more consistent with toxicity rather than with cancer associated retinopathy. The potential for reversibility of the toxicity is unknown. Given the severity of symptoms, we recommend documentation of color vision (and baseline ERG if possible) prior to administration of MGI-114. Supported in part by Research to Prevent Blindness, Inc., New York, New York.
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