TUMOR TREATMENT BY SUSTAINED INTRATUMORAL RELEASE OF CISPLATIN - EFFECTS OF DRUG ALONE AND COMBINED WITH RADIATION

Purpose: The effect of intratumoral delivery of cisplatin to a mouse t umor model (RIF-1) by means of a biodegradable polymer implant with an d without radiation was studied. Methods and Materials: The polymer bi s (p-carboxyphenoxy)propane-sebacic acid (CPP:SA; 80:20) and its degra dation products have been characterized. Polymer rods (8 x 0.5 mm) con taining 17% cisplatin by weight were prepared by extrusion, and the in vitro degradation rate measured. The implants were placed into mouse tumors and their effect (with and without radiation) on tumor growth d elay studied. The levels of Pt in the mouse kidney, tumor, and blood p lasma at selected intervals after implant were also determined. These results were compared with those obtained when cisplatin was delivered systemically. Results: When cisplatin was delivered by the polymer im plants, higher levels were present in the tumor for longer time period s (cf. systemic delivery of the drug). For both nonirradiated and irra diated tumors, those treated with the polymer implants had significant ly longer tumor growth delays compared to nonimplanted controls and to systematically treated tumors. Conclusions: The results show that int ratumoral delivery of cisplatin is more efficient than systemic delive ry. Using the biodegradable polymer implant, higher doses of cisplatin can be tolerated by the animal as the drug is localized within the tu mor, and the high levels of the drug in the tumor can be maintained fo r an extended period of time. When radiation is given in conjunction w ith cisplatin, the tumor response is supraadditive for all modes of ci splatin administration but is potentiated to a greater extent when cis platin is delivered through the polymer implant. The greatest effect i s seen for treatment with cisplatin delivered by polymer implant combi ned with fractionated radiation. (C) 1997 Elsevier Science Inc.