Neutron or photon irradiation for prostate tumors: Enhancement of cytokinetherapy in a metastatic tumor model

We have shown that implantation of human prostate carcinoma PC-3 cells in t he prostates of nude mice led to the formation of prostate tumors with meta stases to para-aortic lymph nodes. We found that day 6 prostate tumors were responsive to systemic injections of interleukin 2 (IL-2) therapy. We have now investigated the combination of primary tumor irradiation and IL-2 for metastatic prostate cancer in this preclinical tumor model. The effect of neutron radiation was compared with that of photon radiation. Advanced pros tate tumors (similar to0.4 cm) were irradiated, and a day later, mice were treated with systemic IL-2 for three weekly cycles. In separate experiments , mire were either sacrificed on day 30 to assess prostate tumor size and t umor histology or followed for survival. A dose-dependent inhibition of pro state tumor growth was caused either by photons or neutrons, but neutrons w ere more effective than photons with a relative biological effectiveness of 2, The tumor inhibition obtained with 250 cGy neutrons and 500 cGy photons was significant (>75%) and was further increased (greater than or equal to 90%) by addition of IL-2 therapy. In survival studies, the combination of radiation and IL-2 showed a significant survival advantage compared with un treated mire (P less than or equal to 0.005) or radiation alone (P less tha n or equal to 0.003) and an increase in median survival compared with IL-2 alone, Histologically, the combined regimen resulted in a greater degree of tumor destruction, inflammatory response, and vascular damage than that ob served with each modality alone. After this combined treatment, no tumor wa s histologically detected in the paraaortic lymph nodes of these mice, and the lymph nodes were significantly smaller. These findings showed that prim ary tumor irradiation, either with neutrons or photons, enhanced IL-2 thera peutic effect for the treatment of advanced prostate cancer. This combined modality induced an antitumor response that controlled the growth of prosta te tumors and their metastases.