Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma

Taxol is a novel antitumor agent with demonstrated efficacy against ovarian, breast, and non-small cell lung cancers in Phase II clinical trials, but which has been shown not to cross the blood-brain barrier. To adapt taxol as a therapy for brain tumors, we have incorporated it into a biodegradable...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-04, Vol.54 (8), p.2207-2212
Main Authors: WALTER, K. A, CAHAN, M. A, AYA GUR, TYLER, B, HILTON, J, COLVIN, O. M, BURGER, P. C, DOMB, A, BREM, H
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Biopolymers
Brain - metabolism
Chemotherapy
Clinical Trials, Phase II as Topic
Decanoic Acids
Drug Implants
Glioma - drug therapy
Glioma - metabolism
Humans
Male
Medical sciences
Paclitaxel - administration & dosage
Paclitaxel - pharmacokinetics
Paclitaxel - therapeutic use
Pharmacology. Drug treatments
Polyesters
Rats
Rats, Inbred F344
Survival Analysis
Tissue Distribution
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Summary:Taxol is a novel antitumor agent with demonstrated efficacy against ovarian, breast, and non-small cell lung cancers in Phase II clinical trials, but which has been shown not to cross the blood-brain barrier. To adapt taxol as a therapy for brain tumors, we have incorporated it into a biodegradable polyanhydride matrix for intracranial implantation and evaluated this formulation in a rat model of malignant glioma. Fischer 344 rats bearing intracranial 9L glioma tumors were treated with 10 mg poly[bis(p-carboxyphenoxy)propane-sebacic acid] (20:80) copolymer discs, containing 20-40% taxol by weight, 5 days after tumor implantation. The taxol-loaded polymers doubled (38 days, 40% taxol loading, P < 0.02) to tripled (61.5 days, 20% taxol loading, P < 0.001) the median survival of rats bearing tumor relative to control rats (19.5 days). Drug loadings of 20-40% taxol by weight released intact taxol for up to 1000 h in vitro. In rats followed up to 30 days postimplant, the polymer maintained a taxol concentration of 75-125 ng taxol/mg brain tissue (100-150 microM taxol) within a 1-3-mm radius of the disc. At points more distant from the disc (up to 8 mm away, the size limit of the rat brain), the polymer maintained a taxol concentration of greater than 4 ng taxol/mg brain tissue (5 microM). We conclude that taxol shows promise as a therapy for malignant glioma when delivered interstitially from a biodegradable polymer.
ISSN:0008-5472
1538-7445