DIPG-65. PRELIMINARY EXPERIENCE OF CHRONIC INTERMITTENT CONVECTION ENHANCED DELIVERY OF CARBOPLATIN AND VALPROIC ACID FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA FOLLOWING RADIATION THERAPY

Diffuse intrinsic pontine glioma (DIPG) is a lethal disease of middle childhood with few treatment options. The failure of chemotherapy is in part due to poor blood-brain barrier penetration. Convection enhanced delivery (CED) uses direct intraparenchymal infusion to distribute drug through target brain volumes. Valproic acid and carboplatin are readily compatible with CED and kill DIPG cells as monotherapies and with synergy when combined. These drugs were combined and translated into a two-day CED treatment schedule for treatment of DIPG on compassionate grounds using a long-term, implantable, drug delivery system (undergoing approval, Renishaw Plc). This device utilises a bone-anchored transcutaneous port for intermittent drug administration without the need for repeated surgery. 9 patients who had previously received radiotherapy were selected for treatment. Surgical implantation of the device was well-tolerated. A total of 27 cycles (54 infusions) of sodium valproate and carboplatin were delivered achieving infusion volumes between 3.6–5.6 mL per infusion. The most common acute infusion-related side-effects included headache and mild limb weakness and all patients were discharged within 24 hours of finishing treatment. We describe our preliminary experience as a prelude to a forthcoming clinical trial.