Thursday, April 4, 2013

Prostate Cancer Vaccine Shows Promise Kate Johnson Mar 21, 2013


MILAN, Italy — A personalized peptide vaccine combined with dexamethasone is significantly more effective than dexamethasone alone in patients with chemotherapy-naïve castration-resistant prostate cancer, investigators report.
"Multiple peptide vaccines were selected on the basis of the patient's immune reaction," said lead investigator Takahiro Kimura, MD, from the Jikei University School of Medicine, Tokyo, Japan. "We think this concept should effectively enhance the pre-existing immune reaction."
The phase 2 study was awarded third prize for the best oncology abstract here at the European Association of Urology (EAU) 28th Annual Congress.
"For a long time, we have not had any milestones in the treatment of castration-resistant prostate cancer," session moderator Tomasz Borkowski, MD, from the Medical University of Warsaw in Poland, told Medscape Medical News. With these vaccines, "we can fight the cancer in a more natural way, not using cytotoxic agents," he explained.
"Dexamethasone is a glucocorticoid known to have antitumor activity for patients with castration-resistant prostate cancer," Dr. Kimura noted. "Peptide vaccines are recognized by antigen-presenting cells, such as dendritic cells, which activate peptide-specific cytotoxic T lymphocyte precursors specific for the pre-existing tumor antigens that exist in the circulation of the patients."
Because the expression profile of tumor antigens is different in every patient, it is necessary to personalize the peptide vaccine.
Dr. Kimura and his team analyzed 71 patients with human leukocyte antigen (HLA) class A02, A24, or A3 and early-stage cancer, defined as a prostate-specific antigen (PSA) level below 10 ng/mL.
Investigators randomized patients to receive dexamethasone 1 mg/day alone or in combination with an individualized multipeptide vaccine, which was given 6 times subcutaneously over a 2-week period.
"Blood samples from patients were evaluated for their immunoreaction to each of 24 candidate of peptides," Dr. Kimura told Medscape Medical News. "A maximum of 4 peptides with high levels of immunoreaction were then administered as a vaccine."
The primary end point of the study was PSA progression, defined by the Prostate Cancer Clinical Trial Working Group as a PSA of at least 25% over nadir or an absolute increase of 2 ng/mL.
PSA response was not significantly different between the vaccine and nonvaccine groups after the first vaccination. However, there was a significantly longer median time to PSA failure in the vaccine group (542 vs 203 days; P = .0008), suggesting "that our peptide vaccination therapy in combination with dexamethasone may be a potential tool for chemotherapy-naïve castration-resistant prostate cancer patients," Dr. Kimura said.
Severe adverse events were not reported in either group, but more patients in the vaccine group experienced injection-site reactions (19 vs 2) and pruritus (11 vs 3).
David Lubaroff, PhD, from the University of Iowa Carver College of Medicine and the Holden Comprehensive Cancer Center in Iowa City, who was asked by Medscape Medical News to comment on the study, said it provides interesting but limited information.
More Work to Be Done
In the past, these vaccines have been reserved for people "with HLA haplotypes associated with the peptides. Usually, these were HLA-A2-associated peptides, which restricted the use of the vaccines to about 50% of the population. This group's use of multiple peptides includes more patients, but still limits its use to 87% of patients," said Dr. Lubaroff.
He added that "the time to PSA failure may not ultimately be the best measure of a treatment's effectiveness. Previous vaccine studies for prostate cancer have demonstrated a lack of correlation between efficacy and time to progression. The best method by which to judge the clinical benefit of vaccine immunotherapy may be overall survival. It will be interesting to follow this group's research to see if dexamethasone plus peptide vaccine therapy will prolong survival."
Dr. Kimura said he agrees that PSA progression is not always a predictor of overall survival. "Most of our patients did not have significant clinical progression and are still living; therefore, we need longer follow-up to assess overall survival," he said.
Although prostate cancer vaccines are "a topic in Europe, it is certainly not new," EAU secretary general Per-Anders Abrahamsson, MD, told Medscape Medical News. He is adjunct professor at the University of Rochester in New York, professor of urology at Lund University, and chair of the Department of Urology at Malmö University Hospital in Sweden.
This study shows another promising tumor vaccine, but Dr. Abrahamsson said he has seen many promising vaccines over the years. "I would like to see more promising data before I truly believe that prostate cancer vaccines will play a major role in the treatment of this common disease," he added.
European Association of Urology (EAU) 28th Annual Congress: Abstract 98. Presented March 16, 2013.

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