PSA velocity was decreased in 74% of those with metastases and 52% of those with only biochemical recurrence. In those with metastases, the high-dose group (n = 10) compared with the low-dose group (n = 24) had improved PSA velocity response (80%

response vs 67% response), time to progression (3.7 months vs 2.3 months), and overall survival (34.9 months vs 24.0 months; P = .33) (Figure 2). Although this survival advantage was not statistically Inhibitors,research,lifescience,medical significant, the expected median survival of the metastasis group was 19.5 months. Subsequently, the GVAX program was halted when a phase III study demonstrated no survival benefit in the GVAX arm when compared with decetaxol in patients with metastatic hormone Inhibitors,research,lifescience,medical refractory disease. Figure 2 (A)Progression-free survival and (B) overall survival in hormone-refractory prostate cancer patients receiving high-dose versus low-dose GVAX prostate cancer vaccine. Reproduced with permission from Small EJ et al.21 Other allogenic tumor cell vaccines have been evaluated in phase I trials. Michael and colleagues22 used 3 cell lines (LnCaP, P4E6, and OnyCap23) to vaccinate 26 men with HRPC and no detectable metastases.

Each patient received 8 × 106 irradiated cells from each cell line combined in 1 vaccine, with the first 3 doses occurring at 2-week intervals and then Inhibitors,research,lifescience,medical monthly for a total of 12 months. BCG was used as an adjuvant for the first 2 doses. The vaccine was well tolerated, with grade 1 to 2 local site reactions, arthralgias, rash, and gastrointestinal

symptoms. Eleven patients (42%) had statistically significant decreases in PSA level. Median time to disease Inhibitors,research,lifescience,medical progression was 58 weeks, compared with 28 weeks in historical controls. More recently, Brill and coworkers23 performed a dose-escalating phase I trial using LnCaP cells transfected with IL-2 and interferon γ. A total of 6 men with metastatic HRPC were treated in 2 dose groups. Inhibitors,research,lifescience,medical Of the 3 high-dose patients, 2 had a greater than 50% decrease in PSA. The time to PSA progression in Phosphoprotein phosphatase these 2 patients was 322 and 693 days. The promising results in these initial investigations support the utility of tumor cell vaccines in prostate cancer treatment. Viral Vaccines Gene therapy has merged with immunotherapy to induce check details immunoreactivity and antitumoral response in patients with prostate cancer. The approaches used in this merger have included both DNA and viral vaccines, and often immunomodulatory agents have been added to amplify the response. The most extensive studies in this area have been PSA-based vaccines. The fact that PSA has localized expression to the prostate and increased levels in most prostatic adenocarcinomas makes it a prime target, though its expression in normal tissues leads to tolerance. Such tolerance needs to be overcome to develop an effective immune reaction.