THE POTENTIATION OF THE EFFECT OF RADIATION TREATMENT BY INTRATUMORALDELIVERY OF CISPLATIN

Purpose: To compare potentiation of the effects of acute or fractionat ed radiation by cisplatin when the drug was delivered intratumorally b y implanted biodegradable polymer, by intraperitoneal injection, or by intraperitoneal osmotic pump. Methods and Materials: Radiation was de livered to a mouse tumor (RIF-1) either in a single dose or in a fract ionated regime in conjunction with cisplatin delivered either asa bolu s injection, with an osmotic pump, or with a biodegradable polymer rod containing cisplatin. The osmotic pump was implanted in the intraperi toneal cavity of the mouse while the polymer implants were placed dire ctly in the tumor. As the polymer degrades, the drug is released at th e treatment site leading to high local concentrations. The osmotic pum p, in contrast, leads to prolonged systemic exposure to the drug at lo w concentrations. Tumor growth delay (TGD) was used as an endpoint in these experiments. Results: The most effective treatment protocol,in t erms of potentiating the effects of radiation was cisplatin delivered by polymer implanted 2 days before an acute dose of radiation (growth modification factor [DMF] = 2.2). Comparison of single and multifracti on regimes where polymer implant was on the same day as the commenceme nt of treatment showed greater potentiation of the effect of fractiona ted than of acute radiation treatment,vith the DMF for fractionated tr eatment remaining relatively constant (1.5-1.9) for 5, 8, and 12 fract ion treatments. Cisplatin delivered via the osmotic pump did not deliv er a high enough dose of cisplatin to produce therapeutic effect in th is mouse tumor model and had little impact on response to treatment. C onclusions: Our results indicated that cisplatin delivered intratumora Ily by biodegradable polymer implant was effective in potentiating the effect of both acute and fractionated radiation. For the fractionated treatments the effect was maintained with increasing fraction numbers and treatment time. (C) 1998 Elsevier Science Inc.