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 60Co gamma rays, and the source of interstitial radiation was implanted 125I 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