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.