Abstract
Glioblastoma Multiforme –(GBM) are infiltrative, impossible to resect totally and consequently recur almost always at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur. Systemic treatment is hampered by the inability of many therapeutic agents to effectively cross the blood brain barrier and systemic toxicity, hence, loco- regional strategies aim to focus drug delivery within the resected tumour cavity wall. Implantable polymers releasing chemotherapeutic agents into the CNS, such as Gliadel® wafers, are a proven example of this approach. Here we report on the first evaluation in humans of the intraparenchymal injection of microspheres containing the topoisomerase II inhibitor irinotecan (Irinotecan Drug-eluting Beads, or IDEB) into the resection cavity after surgical resection of recurrent GBM. The drug-eluting beads (DEBs) used in this study are composed of a biocompatible biomedical polymer hydrogel loaded with chemotherapeutic agent. This drug delivery system is based on a product that is currently approved and available commercially- DC Beads™ that have a defined release characteristics. Irinotecan itself has demonstrated clinical efficacy in treating glioblastoma but with marked systemic drug-related toxicity. It was therefore considered logical that the combination of these products in the IDEB might offer a useful low-risk alternative therapy for patients, providing an improved method of delivery for an efficacious drug. METHODS: 10 Patients with single focus recurrent GBM Suitable for surgery were selected. 100mg of Irinotecan in 3ml was implanted with ~30 injections into resection margin to a depth of 1 cm in 100μ l per injection. Patients were assessed for clinical toxicity (CTC 3) immediately and over 6/12 for SAE, and MRI changes. Plasma Irinotecan levels and steroid use were recorded RESULTS: 9 patients underwent the treatment. There were no major early or late SAE despite the injection process. Wound healing was unaffected and imaging shows no overt brain swelling unlike other depot therapies. One patient had an increased seizure frequency for a few days. Steroid requirements were not increased overall or by comparison with resection only patients. Median survival was 228days with one patient still surviving. Plasma levels were negligible. CONCLUSION: This novel form of therapy using this bead/drug combination, can be simply and safely delivered to patients following resection for recurrent tumour with low risk of wound problems or tumour/brain swelling at these high concentrations of Irinotecan. Future work will establish a maximally tolerated dose delivered in this way