Interstitial chemotherapy of experimental brain tumors: Comparison of intratumoral injection versus polymeric controlled release

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 conclude 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.