Sensitization to radiation from an implanted 125I source by sustained intratumoral release of chemotherapeutic drugs

We have investigated tumor response to low-dose-rate irradiation from an implanted 125I source alone or in conjunction with intratumoral drug administration. The drug (cis-DDP or 5-FU) was incorporated homogeneously into the co-polymer CPP-SA, 20:80, and the polymer/drug rods were implanted in the RIF-1 fibrosarcomas growing subcutaneously in C3H mice. Twenty-four hours later, the tumor was implanted with an 125I seed. Tumor growth time was the end point in these experiments. For implanted 125I sources of different dose rates and implant times giving a range of total doses, a consistent dose-response relationship was shown between tumor growth time and total dose. In other experiments, 125I sources of different specific activities were implanted for periods of time adjusted so that the total dose to the tumor was always the same. When the 125I implant was combined with 5-FU, greater than additive responses were seen for both short (30 h) and long (96 h) 125I treatment times. In contrast, a short-duration (30 h) 125I implant combined with cis-DDP was the least effective treatment, giving a combined response that was no better than additive, whereas 96 h exposure to 125I combined with cis-DDP was the most effective combined treatment. It is conjectured that this inverse dose-rate effect seen when cis-DDP is combined with low-dose rate radiation is related to a cell cycle effect and/or to inhibition of repair of radiation damage by cis-DDP.