Document Detail

Effects of drug efflux on convection-enhanced paclitaxel delivery to malignant gliomas: technical note.
MedLine Citation:
PMID:  17986926     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Convection-enhanced delivery (CED) is an approach in local brain tumor treatment. The spread of infusate in CED can be thought of as involving three phases: backflow, convection, and diffusion. Uncontrolled backflow may lead to efflux of the infusate outside the cranium. METHODS: Based on an interim analysis of a clinical trial, the effects of drug efflux on convection were assessed. In a Phase I/II trial, eight patients with recurrent glioblastomas were treated with CED of paclitaxel. The first group of patients was treated with paclitaxel at a concentration of 0.5 mg/ml according to previously approved protocols. RESULTS: These Group 1 patients developed severe skin necrosis due to an efflux of paclitaxel out of the cranium. The average volume of distribution (Vd) in these patients was 12.8 cm. To prevent paclitaxel efflux, the burr hole was sealed with bone wax during and after CED in Groups 2 and 3. Surprisingly, patients in Group 2 showed a larger Vd (22.9 cm per catheter), exceeding the boundaries of the previous tumor, which led to subsequent neurological deficits. To allow a large Vd without severe side effects, the infusion volume was maintained, but the concentration of paclitaxel was reduced (paclitaxel concentration in Group 3, 0.25 mg/ml). CONCLUSION: Vd remained high and no adverse effects were seen in Group 3. Sealing the burr hole during CED prevented efflux. The simple measure of sealing seems to increase Vd. These data demonstrate that uncontrolled backflow may have an important impact on CED and must be avoided.
Philipp G Tanner; Markus Holtmannspötter; Jörg-Christian Tonn; Roland Goldbrunner
Related Documents :
11114576 - Successful use of central venous catheter as permanent hemodialysis access: 84-month fo...
17986926 - Effects of drug efflux on convection-enhanced paclitaxel delivery to malignant gliomas:...
8333306 - Effect of recombinant tissue plasminogen activator on clot lysis and ventricular dilata...
16082306 - Percutaneous cholecystostomy using a central venous catheter is effective for treating ...
6316826 - Neurologic abnormalities of lyme disease: successful treatment with high-dose intraveno...
20420586 - Efficacy and safety of tafluprost 0.0015% versus latanoprost 0.005% eye drops in open-a...
Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Comparative Study; Journal Article    
Journal Detail:
Title:  Neurosurgery     Volume:  61     ISSN:  1524-4040     ISO Abbreviation:  Neurosurgery     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-11-07     Completed Date:  2007-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7802914     Medline TA:  Neurosurgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E880-2; discussion E882     Citation Subset:  IM    
Department of Neurosurgery, Klinikum Grosshadern, University of Munich, Munich, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Brain Neoplasms / drug therapy,  metabolism*
Drug Delivery Systems / methods
Glioma / drug therapy,  metabolism*
Infusions, Intralesional / methods*
Middle Aged
Paclitaxel / administration & dosage,  pharmacokinetics*
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Ectopic suprasellar growth hormone-secreting pituitary adenoma: case report.
Next Document:  In vivo use of a nanoknife for axon microsurgery.