Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a phase I/II clinical study.
OBJECTIVE
A minority of patients with recurrent glioblastomas multiforme (GBMs) responds to systemic chemotherapy. The authors investigated the safety and efficacy of intratumoral convection-enhanced delivery (CED) of paclitaxel in patients harboring histologically confirmed recurrent GBMs and anaplastic astrocytomas.


METHODS
Fifteen patients received a total of 20 cycles of intratumoral CED of paclitaxel. The patients were observed daily by performing diffusion-weighted (DW) magnetic resonance (MR) imaging to assess the convective process and routine diagnostic MR imaging to identify the tumor response. Effective convection was determined by the progression of the hyperintense signal within the tumor on DW MR images, which corresponded to a subsequent lytic tumor response displayed on conventional MR images. Of the 15 patients, five complete responses and six partial responses were observed, giving a response rate of 73%. The antitumor effect was confirmed by one biopsy and three en bloc resections of tumors, which showed a complete response, and by one tumor resection, which demonstrated a partial response. Lack of convection and a poor tumor response was associated with leakage of the convected drug into the subarachnoid space, ventricles, and cavities formed by previous resections, and was seen in tumors containing widespread necrosis. Complications included transient chemical meningitis in six patients, infectious complications in three patients, and transient neurological deterioration in four patients (presumably due to increased peritumoral edema).


CONCLUSIONS
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.
Lidar
Zvi
Z
Department of Neurosurgery, Advanced Technology Center, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
Mardor
Yael
Y
Jonas
Tali
T
Pfeffer
Raphael
R
Faibel
Meir
M
Nass
Dvora
D
Hadani
Moshe
M
Ram
Zvi
Z
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018481:Convection; D038524:Diffusion Magnetic Resonance Imaging; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000601:surgery; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D010296:Parietal Lobe / Q000473:pathology / Q000601:surgery; D011446:Prospective Studies; D013702:Temporal Lobe / Q000473:pathology / Q000601:surgery
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel