Systemic temozolomide combined with loco-regional mitoxantrone in treating recurrent glioblastoma

Abstract

Twenty-two recurrent GBM patients were enrolled for second tumor debulking with local positioning of a Rickam reservoir, in order to locally deliver chemotherapy with the aim of controlling local tumor recurrence. We designed a protocol using systemic temozolomide (150 mg/sqm days 1-5 every 28) in association with mitoxantrone, delivered through the reservoir (4 mg/day 1-5 every 28) positioned into the area of tumor exeresis. After re-operation a residual tumor mass no larger than 2 cm was identified in 18/22 patients. The patients were treated with monthly cycles of chemotherapy until evolution of the tumor, but in no case for more than 10 cycles. Responses were evaluated by MRI scans performed every 2 months and images assessed according to MacDonald's criteria. Response rate: no complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive disease (PD) occurred. The median progression-free survival (PFS) and survival time (ST) of the whole group of treated patients was 7 and 11 months, respectively and more than a quarter of the patients survived over 18 months. During the study, the patients' compliance was complete and no dropouts occurred. Hematological toxicity was mild and after repeated local injections only minor neurological side-effects occurred. Despite some bias in patients' selection not excluded in this pilot study, results are interesting: the PFS was as long as the survival of recurrent GBM reported in the literature.