LG-52THEOPHYLLINE IN VISION IMPAIRED CHILDREN WITH OPTIC PATHWAY GLIOMA

LG-52. THEOPHYLLINE IN VISION IMPAIRED CHILDREN WITH OPTIC PATHWAY GLIOMA Gail Halliday, Peter Ling, Michal Zapotocky, Arun Reginald, Uri Tabori, Iris Fried, Eric Bouffet, Lee Dupuis, and Ute Bartels; The Hospital for Sick Children, Toronto, ON, Canada PURPOSE: Preclinical models suggest that phosphodiesterase inhibitors may slow or prevent axonal damage to the optic nerve in mice with visual pathway glioma likely through elevation of cAMP. A feasibility study was performed to evaluate the safety and efficacy of theophylline in vision impaired children with optic pathway glioma (OPG) at risk of visual loss. METHODS: Patients were treated with theophylline for a planned duration of 12 months. Eight of the eleven patients received concurrent standard OPG chemotherapies. The initial theophylline dose was calculated based on ideal body mass and subsequently adjusted according to trough serum levels. The primary end point was safety, defined by grade 3-4 toxicity using the National Cancer Institute Common Toxicity Criteria version 4.0. Secondary end points included visual acuity response rate. RESULTS: Preliminary data analysis of eleven patients, with a median age of 9.2 years, treated with theophylline at the Hospital for Sick Children, Toronto between 2009 and 2015 is detailed here. After a mean duration of 10.5 months no grade 3-4 treatment related toxicities were identified. Of the three patients who discontinued therapy prematurely two experienced grade 1 toxicities. Three of eleven patients studied showed improvements in binocular vision whilst on theophylline therapy with a further three patients showing stabilization of vision. CONCLUSIONS: Combining theophylline with standard chemotherapies for OPG in children is safe and feasible. In a proportion of patients with progressive visual decline despite prior chemotherapy theophylline enabled stabilization or improvement in visual acuity. Phase III proof of efficacy trials are warranted. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.52 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.