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A Preclinical Study of Combination Therapy Using Radiation Therapy with 5-Aminolevulinic Acid and Carbamide Peroxide

J Panetta*, D Cvetkovic , L Chen , C Ma , Fox Chase Cancer Center, Philadelphia, PA


(Thursday, 8/2/2018) 7:30 AM - 9:30 AM

Room: Karl Dean Ballroom A1

Purpose: This work aims at a novel treatment technique that uses high energy radiation in combination with photosensitizers to achieve tumor control in deep seated tumors. The purpose of this study is to investigate the synergetic effect of radiotherapy (RT), specifically combined with 5-aminolevulinic acid (5-ALA) as a generator of photosensitizing porphyrins and carbamide peroxide as a generator of oxygen species, relative of RT using a mouse model.

Methods: Male nude mice were injected with human prostate cancer (PC-3) cells subcutaneously bilaterally into their flanks. Animals with tumors ranging from [25-1660 mm³] were randomized into three groups: a control group that was left untreated (n=23), a group treated with RT (15MV, 4Gy, n=26), and a group treated with RT+sensitizers (n=16), which consisted of a tail-vein injection of 100 mL/kg of 5-ALA administered ~4 hours prior to RT, as well as injection of 60 mL/kg of carbamide peroxide directly into one of the tumors of the mice immediately before RT (15MV, 4Gy). Efficacy was monitored with weekly MR scans using a GE Signa 1.5 T MR scanner, followed by analysis of tumor volume.

Results: Tumors treated with RT plus 5-ALA/carbamide peroxide increased 2.80±0.18%, compared with an increase of 3.77±0.45% for RT only and of 4.36±0.67% for the control group. Each of the groups displayed a wide range in response: [1.39%–4.02%], [1.55%–11.81%] and [1.23%–12.31%] for the combination therapy, RT alone and control groups, respectively. Within the combination therapy and RT groups, 87% and 62%, respectively, of the tumors responded better than the mean response of the control group. Moreover, no significant differences were found when the tumors were grouped according to initial size.

Conclusion: RT combined with 5-ALA and carbamide peroxide resulted in a more significant tumor growth delay compared to both RT alone and no treatment in this preliminary study.


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