Injectable chemotherapeutic microspheres and glioma II: Enhanced survival following implantation into deep inoperable tumors

Purpose. Delivery of chemotherapeutics using implantable, biodegradable pol ymers provides a potentially powerful method of treating brain tumors. The present studies examined the ability of injectable microspheres, formulated to release carboplatin or BCNU for 2-3 weeks, to enhance survival in a rod ent model of deep, inoperable glioma. Methods. Rat glioma (RG2) cells were implanted into the striatum of rats. I n a first experiment, the tumors were allowed to grow for 3 days, followed by either no treatment, bolus chemotherapy (100 mu g), or implantation of m icrospheres containing 10, 50, or 100 mu g of carboplatin. The microspheres were implanted, via hypodermic injection, directly into the center of the small, 3-day-old tumors. In a second experiment, tumors grew for 8 days pri or to treatment with either carboplatin- or BCNU-loaded microspheres. The m icrospheres were then injected either directly into the center of these lar ger tumors or into three sites along the perimeter of the tumor. Separate s ets of animals received bolus chemotherapy (100 mu g) into either the tumor center or around the tumor perimeter. Results. Injection of carboplatin-loaded microspheres into the center of th e small 3 day old, tumors produced dose-related increases in survival. When injections of carboplatin- or BCNU-loaded microspheres were made into the center of the larger, 8-day-old tumors, survival was not enhanced. However, when the microspheres were injected along the perimeter of the larger tumo rs, sustained-release chemotherapy did significantly prolong survival. Bolu s chemotherapy was less effective than sustained release chemotherapy. Conclusions. Together, these data: (1) demonstrate that sustained delivery of chemotherapy in or near the tumor site is superior to equipotent bolus d oses in inoperable tumors, (2) demonstrate that injection of sustained rele ase microspheres into the tissue surrounding a growing tumor may provide su perior effects over injections directly into the tumor mass, and (3) sugges t that this approach may provide a useful means of selectively delivering c hemotherapeutics to tumors or portions of tumors that cannot otherwise be t reated with conventional surgical approaches.