Immunotherapy May Boost Prostate Cancer Response to Hormone Therapy

NEW YORK JULO 21, 2008 (Reuters Health) - Patients with nonmetastatic castration-resistant prostate cancer (stage D0.5) treated with an experimental vaccine targeting prostate specific antigen (PSA) subsequently showed clinical response to second-line hormone therapy, according to a long-term follow-up study of a phase II clinical trial.

The original trial included 42 previously treated patients with rising serum PSA despite castrate levels of testosterone (< 50 ng/dL) with no radiographic evidence of metastases.

The patients were randomly assigned to initial treatment either with the androgen receptor antagonist nilutamide (300 mg/day for 1 month followed by 150 mg/day thereafter) or with a poxvirus-based PSA vaccine.

The vaccine regimen included a priming vaccine on day 1 (recombinant poxvirus carrying transgenes for PSA and for the human T-cell co-stimulatory molecule B7-1) followed by monthly booster vaccines. Vaccinations were accompanied by treatment with granulocyte-macrophage colony-stimulating factor and interleukin 2.

In both treatment arms, if serum PSA rose in the absence of metastatic disease, patients were permitted to receive both treatments.

In the July 15 issue of Clinical Cancer Research, Dr. Jeffrey Schlom and colleagues at the National Cancer Institute in Bethesda, Maryland, report survival analyses at 6.5 years from the initiation of therapy (median potential follow-up, 4.4 years).

According to their paper, there was a trend toward longer survival among patients initially assigned to vaccine (median 5.1 vs 3.4 years, p = 0.13). Survival in the vaccine group was particularly favorable among those who had a Gleason score no higher than 7 or PSA < 20 ng/dL at baseline, or who had prior radiation treatment.

Among patients who received both treatments, survival was significantly longer among the 12 initially treated with vaccine than among the 8 treated first with nilutamide (median 6.2 vs 3.7 years, p = 0.045).

The investigators theorize that "vaccine therapy initiates a dynamic process of host immune responses that can be exploited in subsequent therapies."

Dr. Schlom"s group is currently enrolling patients in a trial of a next-generation poxviral vaccine consisting of PSA plus three costimulatory molecules (B7-1, lymphocyte function associated antigen-3, and intercellular adhesion molecule 1).

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