Details

Autor(en) / Beteiligte

• GULLEY, James L
• ARLEN, Philip M
• CAMPHAUSEN, Kevin
• COLEMAN, C. Norman
• SULLIVAN, Francis
• STEINBERG, Seth M
• SCHLOM, Jeffrey
• DAHUT, William
• BASTIAN, Anne
• MORIN, Steven
• MARTE, Jennifer
• BEETHAM, Patricia
• TSANG, Kwong-Yok
• YOKOKAWA, Junko
• HODGE, James W
• MENARD, Cynthia

Titel

Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer

Ist Teil von

• Clinical cancer research, 2005-05, Vol.11 (9), p.3353-3362

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. Experimental Design: We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a “priming” vaccine with recombinant vaccinia (rV) PSA plus r V containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. Results: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm ( P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. Conclusion: This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.