Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a Phase I/II clinical study

Abstract

On the basis of our data we suggest that CED of paclitaxel in patients with recurrent malignant gliomas is associated with a high antitumor response rate, although it is associated with a significant incidence of treatment-associated complications. Diffusion-weighted MR images may be used to predict a response by demonstrating the extent of convection during treatment. Optimization of this therapeutic approach to enhance its efficacy and reduce its toxicity should be explored further.

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

“…It has been proposed that this complication is caused by subcutaneous leaking of paclitaxel, which interferes with adequate wound healing (29). In our study one animal in every group experienced suture dehiscence, but a complete response was obtained after wound irrigation and antibiotic therapy.…”

“…All other animals treated with 20 mg/kg had no neurologic complications. Clinical studies using CEDD of paclitaxel showed a similar complication, which was attributed to leakage of paclitaxel into the subarachnoid space (29). Accidental intrathecal administration of other anti-microtubule agents has been shown to produce a wide range of complications and should be avoided (31,32).…”

“…The results of a phase II study of locally-delivered paclitaxel using convection-enhanced drug delivery (CEDD) for treatment of patients with recurrent glioblastoma multiforme were recently published and showed that paclitaxel administered via CEDD had marked anti-tumor responses but generated a significant incidence of treatment-associated complications (29). The delivery of paclitaxel via CEDD and its effect within the tumor can be monitored clinically usingdiffusion-weighted magnetic resonance imaging (DW-MRI) (30).…”

Imaging in neurooncology

“…120,121 In trials employing convection-enhanced delivery of local chemotherapeutics, DWI is being used to assess the convective process and routine diagnostic MR imaging to identify the tumor response. 132 …”

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and paclitaxel have cooperative in vivo effects against glioblastoma multiforme cells

“…Paclitaxel was investigated in a phase II study in GBM and found to be well tolerated (3). More recently, convectionenhanced delivery of paclitaxel for treatment of recurrent malignant glioma has been studied in a phase I/II clinical trial (4). Furthermore, newer formulations of paclitaxel are also being investigated preclinically for treatment of glioma, including Oncogel, a controlled-release depot formulation of paclitaxel that can be directly applied to local areas within the brain (5).…”