TY - JOUR
T1 - Interstitial Taxol Delivered from a Biodegradable Polymer Implant against Experimental Malignant Glioma1
AU - Walter, Kevin A.
AU - Cahan, Mitchell A.
AU - Gur, Aya
AU - Tyler, Betty
AU - Hilton, John
AU - Colvin, O. Michael
AU - Burger, Peter C.
AU - Domb, Abraham
AU - Brem, Henry
PY - 1994/4/15
Y1 - 1994/4/15
N2 - 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 μM 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 μM). We conclude that taxol shows promise as a therapy for malignant glioma when delivered interstitially from a biodegradable polymer.
AB - 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 μM 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 μM). We conclude that taxol shows promise as a therapy for malignant glioma when delivered interstitially from a biodegradable polymer.
UR - http://www.scopus.com/inward/record.url?scp=0028350677&partnerID=8YFLogxK
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C2 - 7909720
AN - SCOPUS:0028350677
SN - 0008-5472
VL - 54
SP - 2207
EP - 2212
JO - Cancer Research
JF - Cancer Research
IS - 8
ER -
