Neutron or Photon Irradiation for Prostate Tumors: Enhancement of Cytokine Therapy in a Metastatic Tumor Model

• Published in: Clinical cancer research Vol. 7; no. 1; pp. 136 - 144
• Main Authors: HILLMAN, Gilda G, MAUGHAN, Richard L, GRIGNON, David J, YUDELEV, Mark, RUBIO, Johanna, TEKYI-MENSAH, Samuel, LAYER, Andrey, MINGXIN CHE, FORMAN, Jeffrey D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.01.2001
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - radiotherapy; Animals; Antineoplastic agents; Biological and medical sciences; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Dose-Response Relationship, Radiation; Humans; Injections, Intravenous; Interleukin-2 - therapeutic use; Male; Medical sciences; Mice; Neoplasm Recurrence, Local; Neutrons; Pharmacology. Drug treatments; Photons; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - radiotherapy; Radiation Tolerance; Radiotherapy, Conformal - methods; Time Factors; Treatment Outcome; Tumor Cells, Cultured - radiation effects; Antineoplastic agent; Animal model; Carcinoma; Prostate disease; Metastasis; Dose activity relation; Photon irradiation; Interleukin 2; Immunotherapy; Male genital diseases; Urinary system disease; Lymph node; Treatment efficiency; Rodentia; Cytokine; Malignant tumor; Radiotherapy; Survival; Vertebrata; Mammalia; Treatment; Mouse; Animal; Neutron irradiation; Metastatic; Combined treatment; Prostate; Comparative study
• ISSN: 1078-0432; 1557-3265

We have shown that implantation of human prostate carcinoma PC-3 cells in the prostates of nude mice led to the formation of prostate tumors with metastases 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 prostate tumors (∼0.4 cm) were irradiated, and a day later, mice were treated with systemic IL-2 for three weekly cycles. In separate experiments, mice were either sacrificed on day 30 to assess prostate tumor size and tumor histology or followed for survival. A dose-dependent inhibition of prostate tumor growth was caused either by photons or neutrons, but neutrons were 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 (≥90%) by addition of IL-2 therapy. In survival studies, the combination of radiation and IL-2 showed a significant survival advantage compared with untreated mice ( P ≤ 0.005) or radiation alone ( P ≤ 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 observed with each modality alone. After this combined treatment, no tumor was histologically detected in the para-aortic lymph nodes of these mice, and the lymph nodes were significantly smaller. These findings showed that primary tumor irradiation, either with neutrons or photons, enhanced IL-2 therapeutic effect for the treatment of advanced prostate cancer. This combined modality induced an antitumor response that controlled the growth of prostate tumors and their metastases.