Long-term outcome of a phase II trial using immunomodulatory in situ gene therapy in combination with intensity-modulated radiotherapy with or without hormonal therapy in the treatment of prostate cancer
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The objective of this study is to report the long-term outcome of a phase II trial of immune-modulatory in situ gene therapy (GT) in combination with intensity-modulated radiotherapy (IMRT) with or without hormonal therapy for the treatment of prostate cancer.
GT was comprised of intraprostatic injection of adenoviral vector containing herpes simplex thymidine kinase (ADV/HSV-tk) followed by valacyclovir. A mean dose of 76 Gy was delivered to the prostate with IMRT. Low-risk patients (arm A; T1–T2a, Gleason score <7, pretreatment PSA <10) were treated with two injections of ADV/HSV-tk, each followed by valacyclovir, and IMRT. Intermediate/high-risk patients (arm B; T2b–T3, Gleason score ≥7, pretreatment PSA ≥10) were treated with three injections of ADV/HSV-tk, each followed by valacyclovir, IMRT, and hormonal therapy.
Sixty-six patients (33 patients in each arm) were enrolled. The median follow-up was 100 months. Five-year freedom from failure (FFF) rates were 94 and 91 % for arms A and B, respectively. Five-year overall survival (OS) rates were 97 and 94 % for arms A and B. Negative biopsy rates at 24 months were 83 and 79 % for arms A and B. One patient in arm B developed grade 3 elevation in liver enzyme. There was no grade 3 or higher hematologic toxicity. One patient had grade 3 genitourinary toxicity. There was no grade 3 or higher lower gastrointestinal toxicity.
The combination of immunomodulatory in situ gene therapy and IMRT with or without hormonal therapy is feasible, safe, and effective in the treatment of prostate cancer. The effectiveness of this combined approach was likely through enhanced cytotoxicity, antitumor immune response, and abscopal effects. This approach with long term follow up appears to provide better clinical outcome over historical controls. A randomized trial of this strategy is currently ongoing.
KeywordsGene therapy Prostate cancer Hormonal therapy IMRT Immunomodulatory Radiotherapy
This work was supported by a specialized Program of Research Excellence (SPORE) grant (CA58204) from the National Cancer Institute, the Methodist Hospital Foundation, and the General Clinical Research Center (GCRC).
Compliance with ethical standards
This work was supported by NIH SPORE Grant P50-58,204. A specialized Program of Research Excellence (SPORE) grant (CA58204) from the National Cancer Institute, the Methodist Hospital Foundation, and the General Clinic Research Center (GCRC).
Conflicts of interest
The authors declare that they have no competing interests.
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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