Tumor treatment by sustained intratumoral release of 5-fluorouracil: Effects of drug alone and in combined treatments

Purpose: To evaluate an intratumoral polymer implant for sustained delivery of 5-fluorouracil (5-FU) in a mouse tumor model. Methods and Materials: 5-FU was incorporated into a polyanhydride-based polymer, bis(p-carboxyphenoxy)propane sebacic acid (CPP:SA) and implanted in RIF-1 mouse fibrosarcoma growing s.c. The effectiveness of treatment was evaluated by tumor growth delay. External beam radiation was Co-60 gamma rays, and the source of interstitial radiation was implanted I-125 Seeds. A second drug, cis-diamminedichloroplatinum (cis-DDP), was administered by intraperitoneal injection or by osmotic pump. Results: For drug/polymer implant alone, the tumor growth delay was proportional to the amount of drug in the implant. The 5-FU polymer implant was most effective when combined with cis-DDP or with acute or fractionated radiation, and in some cases, the effects of combined treatments were greater than additive. The most effective combination was intratumoral 5-FU and low-dose-rate radiation delivered from an interstitial radiation source. Conclusion: Results indicate that 5-FU can be effectively delivered by polymer implant and that this mode of delivery is particularly appropriate for combined treatments. (C) 2002 Elsevier Science Inc.