Neutron or photon irradiation for prostate tumors: enhancement of cytokine therapy in a metastatic tumor model.
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 (approximately 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 (> or = 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 < or = 0.005) or radiation alone (P < or = 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.
Hillman
G G
GG
Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute at Wayne State University School of Medicine Detroit, Michigan 48201, USA. ghillman@med.wayne.edu
Maughan
R L
RL
Grignon
D J
DJ
Yudelev
M
M
Rubio
J
J
Tekyi-Mensah
S
S
Layer
A
A
Che
M
M
Forman
J D
JD
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009364:Neoplasm Recurrence, Local; D009502:Neutrons; D017785:Photons; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D011836:Radiation Tolerance; D020266:Radiotherapy, Conformal / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D007376:Interleukin-2