The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation

Abstract

A syngeneic, androgen-sensitive Dunning R3327 rat prostatic adenocarcinoma was transplanted bilaterally in the flanks of male Copenhagen Fisher rats. Approximately 3 months after implantation, when the tumours had a median volume of 150 mm3, one group of rats was treated with histamine alone (4 mg kg(-1) subcutaneously on week days), another group with human recombinant interleukin 2 (IL-2) alone (425 IU kg(-1) continuous infusion) and a third group with both histamine and IL-2 during 6 weeks. Tumours on one flank were irradiated (6 Gy once daily for 3 days to a total dose of 18 Gy) beginning 1 week after the onset of treatment with histamine and/or IL-2. The contralateral tumour served as the intra-animal control. The tumour volumes were determined weekly. The growth curves showed that all three drug treatments were effective in delaying growth, but when used individually did not cause tumour shrinkage. Radiation was the most effective single agent, but when used alone the shrinkage did not occur until 2 weeks after irradiation. When combined with the drugs, more rapid and extensive growth delay and/or shrinkage was seen. The growth curves showed clear differences between the different treatments. The combination of the three agents was the most effective of all. The most striking difference between radiation alone and radiation plus biotherapy was the time at which a tumour response was detectable. Thus, active biotherapy alone and especially in a combination with histamine and radiotherapy warrants further investigation as a potential therapeutic approach to prostate cancer.