Experimental study of the intra-operative radiation therapy in pancreatic cancer

The radiosensitivity of pancreatic cancer, optimum dose of irradiation and the effect of 1-[(4'-Hydroxy-2'-Butenoxy) Methyl]-2-Nitrosoimidazole (RK-28) on irradiation were investigated using an experimental pancreatic cancer of hamster and the following results were obtained: i) The mean lethal dose (Do) and the 50% tumor control dose (TCD50) against the pancreatic cancer were 3.5 Gy and 73.7 +/- 6.9 Gy, respectively. These results indicate that the pancreatic cancer is resistant to irradiation, which could be explained by the existence of hypoxic cells consisting of 35% of the tumor. ii) The dose of intraoperative irradiation (10-40 Gy) seemed to be insufficient to bring long-term anti-tumor effect and long-term survival since that dose resulted in only temporary regression of the tumor. iii) The hypoxic cell sensitizer (RK28), which is known to specifically enhance the sensitivity of hypoxic cells to irradiation, lowered TCD50 of the pancreatic cancer to 53.8 +/- 1.57Gy. Therefore, RK-28 was effective in the treatment of the experimental pancreatic cancer (the enhancement ratio: 1.37). When combined with 30 or 40 Gy of irradiation, which is applicable to intraoperative irradiation, RK-28 induced a longer period of tumor suppression and a higher tumor regression ratio than irradiation alone. These results indicate that RK-28 significantly increases the effect of intraoperative irradiation and this combination therapy could possibly induce remarkable effect on tumor regression and long-term survival.