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- Title
923. Combining In Situ Gene Therapy with Radiotherapy and Hormonal Therapy in the Treatment of Stage D1 Prostate Cancer.
- Authors
Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Ayala, Gustavo; Wei-Yuan Mai; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Tabata, Ken-ichi; Aguilar-Cordova, Estuardo; Wheeler, Thomas; Butler, E. Brian; Thompson, Timothy C.
- Abstract
Introduction: Clinical trial of combination adenoviral vector mediated Herpes Simplex Virus-thymidine kinase (HSV-tk) + valacyclovir (VCV) in situ gene therapy with radiotherapy (RT) and hormonal therapy was conducted for Stage D1 prostate cancer. We now report the safety, efficacy, and immune responses using this approach.Methods: Five patients with Stage D1 prostate cancer were treated as follows: Gene therapy: 3 separate intraprostatic injections of AdHSV-tk were performed on days 0, 56, and 70. Each injection was followed by 2 weeks of VCV. RT to pelvic lymphatics and prostate was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy: lupron and flutamide were initiated on day 0 for 4 months or 2 years. Toxicity was assessed using CTEP and RTOG toxicity scores. Peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting (FACS) after the incubation with dual color labeled antibody pairs: CD45/CD14, CD3/CD19, CD3/CD8, CD3/CD4, CD8/HLA-DR, CD4/HLA-DR, CD3/HLA-DR, and CD3/CD56+CD16. PSA, prostate biopsy, and FACS samples were taken at selected intervals. ASTRO consensus definition was used for PSA failure.Results: Median age was 50 years and median follow-up for the entire group was 29 months. Mean and median pre-treatment PSA were 97.3 and 16.9 ng/ml (range; 2.5 – 374 ng/ml). Gleason score was 8 in 2 patients and 9 in the other 3 patients. Three of the 5 patients had biochemical failure at 3, 3, and 7.7 months: 2 patients had distant failure in the bones and 1 patient had failure in the para-aortic lymph nodes outside radiation treatment portal. Prostate biopsies however revealed no evidence of residual carcinoma in all cores. The pre-treatment mean percentages of activated CD8+ (DR+CD8+) T cells and activated CD4+ (DR+CD4+) T cells were 12.0% and 5.3% respectively. Four months after the initial treatment, the mean percentages of DR+CD8+ T cells and DR+CD4+ T cells increased to 32.7% and 18.8% (P = 0.0431) respectively. No grade 3 or higher toxicity was seen. The GU and GI toxicity profiles are no different from those of patients treated with RT alone.Conclusions: We present evidence of safety and efficacy using this combined radio-gene-hormonal therapy approach for Stage D1 prostate cancer. These results also suggest the potential for activation of cell-mediated immune response using this combined therapy. Current efforts are aimed to improve systemic control by maximizing activation of anti-tumor immune response in these patients via radio-gene therapy.Molecular Therapy (2006) 13, S356–S357; doi: 10.1016/j.ymthe.2006.08.1014
- Subjects
GENE therapy; CLINICAL trials; CANCER treatment; CANCER patients; RADIOTHERAPY
- Publication
Molecular Therapy, 2006, Vol 13, pS356
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.1014