Injectable Polymer Depot Combined With Radiofrequency Ablation for Treatment of Experimental Carcinoma in Rat

Abstract

The purpose of this study was to investigate whether an intralesional chemotherapy depot with or without a chemosensitizer could improve the efficacy of radiofrequency (RF) ablation in treatment of experimental carcinoma in rats. Eighteen BD-IX rats were inoculated with bilateral subcutaneous tumors via injection of DHD/K12TRb rat colorectal carcinoma cells in suspension. Four weeks after inoculation, one tumor in each rat was treated with RF ablation at 80 degrees C for 2 minutes and the other with RF ablation followed by intralesional chemotherapy with carboplatin. The drug was administered via 2 different in situ-forming poly(D,L-lactide-coglycolide) (PLGA) depot formulations either with or without a chemosensitizer. Treatment efficacy was assessed by comparing the change in tumor diameter compared with control, percent of coagulation necrosis and a rating of treatment completeness. Tumors treated with ablation and carboplatin + sensitizer (n = 9) showed a diameter decrease of 49.4 +/- 24.5% at the end point relative to ablation control, while those treated with ablation and carboplatin only (n = 8) showed a 7.1 +/- 12.6% decrease. Use of sensitizer also showed increased tissue necrosis (81.9 +/- 9.7% compared with 68.7 +/- 26.7% for ablation only) and double the number of complete treatments (6/9 or 66.7%) compared with ablation control (3/9 or 33.3%). From these results, we conclude that intralesional administration of a carboplatin and sensitizer-loaded polymer depot after RF ablation has the potential to improve the outcome of ablation by increasing effectiveness of local adjuvant chemotherapy in preventing progression of tumor unaffected by the ablation treatment.