The treatment of glioblastomas: a systematic update on clinical Phase III trials

Glioblastomas (GBMs) are invariably associated with unavoidable tumor recurrence and overall poor prognosis. The present study is to summarize the results of clinical Phase III studies on GBMs over the past seven years. A systematic literature search was performed using major electronic databases and by screening meeting abstracts. Totally, 16 studies of patients with newly diagnosed GBMs, recurrent GBMs, and elderly patients with GBMs were selected for this review. Although the outcomes of the experimental therapies were not encouraging, these studies produced a considerable amount of potentially clinically relevant information. Such aspects as surgical outcomes, radiation schedules, temozolomide (TMZ) schedules, methylation status of the O6-methylguanine DNA methyltransferase (MGMT) gene, combination of therapies, novel drug delivery methods and use of targeted agents have come to light and are being addressed here. In addition, we discuss the existing controversies of (1) surgical studies, (2) evaluations of recurrence, (3) salvage treatment bias, and (4) studies on elderly patients.