The autologous cellular immunotherapy sipuleucel-T (Provenge) can be safely given prior to radical prostatectomy, and in the neoadjuvant setting, the vaccine exerts a favorable effect on immune cells in prostate cancer tissue, specifically at the interface between the benign and malignant glands.
"This is an off-label use of sipuleucel-T as a study. We wanted to see if it can be given safely and early in the course of prostate cancer, and whether we can induce an immune response similar to what we induce in castration-resistant prostate cancer," said lead author Lawrence Fong, MD, associate professor of hematology/oncology at the University of California, San Francisco Comprehensive Cancer Center.
Thirty-eight of 42 patients (90%) received all three pre-op infusions of the vaccine; three received two infusions, and one received no infusions. Immunohistochemistry analysis was completed on 25 patients for CD3 and CD8 expression and on 23 for CD4 and Fox P3 expression.
Results showed a greater-than threefold increase in mean CD3+ and CD3+/CD4+ cells per area as well as a twofold to threefold increase in CD3+/CD8+ cells/area at the prostatectomy interface compared with pre-treatment biopsy, prostatectomy tumor, and benign tissue. Regulatory T-cells (CD3+/CD4+/FoxP3+ cells) were also increased at the tumor interface, but represent a small population of the observed T cells.
Tx does not appear to affect surgery
Within less than 24 hours after pre-prostatectomy sipuleucel-T infusion, the following adverse events were reported in >5% of patients: fatigue (36%), headache (17%), myalgia (12%), arthralgia (10%), and chills (7%). One serious adverse event (infusion-related reaction) was reported. There did not appear to be any impact of sipuleucel-T on surgery, Dr. Fong said.
"This is an exciting abstract," commented Nicholas Vogelzang, MD, medical oncologist at the Comprehensive Cancer Centers of Nevada, Henderson, and chair and medical director of the developmental therapeutics committee of U.S. Oncology Research, who was not involved with the study. "This abstract showed at a cellular level that immune cells are penetrating into cancer.
Dr. Vogelzang said this study provides proof of principle for studying the vaccine earlier in the course of prostate cancer. A study is now under way in patients with rising PSA after radical prostatectomy or radiotherapy comparing sipuleucel-T given before and after hormone therapy.
Dr. Fong and several of his co-authors have received research funding, honoraria, and/or other remuneration; have an employment or leadership position; and/or own stock in Dendreon Corp.