Interstitial
chemotherapy with controlled release
polymers is a clinical adjunct in the management of
malignant gliomas. The need for
polymer to release the chemotherapeutic
drug rather than simply injecting the
drug into the
tumor warrants further investigation. Therefore, we compared the effects of direct
intralesional injection of
carmustine (
BCNU) and
4-hydroperoxycyclophosphamide (4HC) into the rat
brain tumor bed with those from the same agents delivered via controlled release
polymers implanted intracranially. Treatment was initiated on the fifth day after intracranial implantation of 9L
gliosarcoma into male rats; two doses of each
drug were injected intratumorally, representing either the amount of
drug typically released in vivo from
polymer during the first 24 h, or the maximal
drug loaded on each
polymer. Control rats were treated with empty
polymers. We found that the median lifespan was extended in the groups of rats treated with intratumoral injection of
BCNU (23% and 36% for 1 mg and 2 mg doses), and 271% with
BCNU-impregnated
polymer. Similar results were found with intratumoral 4HC (21% and 36% for 0.1 mg and 2 mg injection doses), and 121% with 4HC-impregnated
polymer. Overall survival after intraneoplastic
injections, however, was not statistically significantly different from that of control rats (p > 0.05). Furthermore, improvement in survival was not consistent, and some animals subjected to 4HC injection died early in the course of treatment. Polymeric treatment resulted in statistically significant prolongation of survival, compared to control rats (p < 0.001 for both
BCNU and 4HC). We concluded that direct
intralesional injection of
BCNU and 4HC is less effective than controlled release via
polymers for the treatment of 9L
gliosarcoma in the rat model.