Posted 2/6/2012 10:12 PM (GMT 0)
[The article did not consider the cost.]
Vaccine Eyed for Early-Stage Prostate Ca
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: February 04, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
Action Points
Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Explain that the immunotherapy agent sipuleucel-T (Provenge) appears safe for use earlier in prostate cancer.
Point out that the trial also confirmed the expected immune-cell responses when given outside of the approved setting in patients with metastatic prostate cancer.
SAN FRANCISCO -- The immunotherapy agent sipuleucel-T (Provenge) appears safe for use earlier in prostate cancer, researchers found.
Neoadjuvant treatment in localized prostate cancer didn't impact surgery or complications, though one of the 42 patients in the phase II trial experienced a serious infusion reaction, Lawrence Fong, MD, of the University of California San Francisco, and colleagues reported.
The trial also confirmed the expected immune-cell responses when given outside of the approved setting in patients with metastatic prostate cancer.
"What this opens the door to, far down the road, is perhaps taking high-risk patients and maybe pretreating them with sipuleucel-T to help their immune system recognize cancer before it has the chance to metastasize," commented Leonard Gomella, MD, of Thomas Jefferson University in Philadelphia and chair of the conference program committee.
That early stage setting theoretically is where the prostate cancer vaccine would work best, Fong noted in an interview with MedPage Today. "Men with more limited cancer will be less immune compromised," he explained.
Sipuleucel-T therapy involves collecting a patients' own peripheral white blood cells, which undergo ex vivo treatment to induce recognition and reaction to tumor cell antigens, and then infused back as a mix of activated and antigen-presenting cells.
The theory that this treatment induces an immune attack on the tumor has been suggested by post-treatment blood samples showing an uptick in certain types of immune cells, but advanced prostate cancer doesn't offer ready opportunities for biopsy to confirm an impact on the tumor itself.
Giving the therapy six to eight weeks before radical prostatectomy provided a unique opportunity to evaluate the tumor after treatment.
Testing these samples from the 42 men who received three open-label infusions of sipuleucel-T before their surgery in the NeoACT P07-1 study turned up the following results (all P<0.001):
At least a three-fold increase in mean CD3+ and CD3+/CD4+ cell concentration at the tumor surface compared with pretreatment biopsy and normal prostate tissue taken out with the tumor
A two- to three-fold increase in CD3+/CD8+ cell concentration at the tumor surface compared with pretreatment biopsy and noncancerous prostate tissue collected during surgery
An increase in regulatory T cells at the tumor interface
"These T cells that we think may be responsible for how Provenge works actually are at the tumor site," Fong explained. "So it gives us a sense that the treatment can alter the immune system's response at the level of the tumor."
While it's too early to say whether sipuleucel-T treatment will have any impact on prostate cancer recurrence, progression, or survival, Fong said his group plans to continue to follow these patients' outcomes.
And another presentation of the study results at the same session showed that the immune system remained activated after radical prostatectomy.
The next step will be to see what impact the vaccine has on localized prostate cancer in the watchful waiting setting without surgery.
"Now that we see an immune response is there, it gives us some support to pursue such a strategy," Fong noted.
Gomella cautioned that these proof of principle findings should not be translated to the clinic without additional study results.
The symposium was sponsored by ASCO, the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology.
The study was sponsored by Dendreon.
Fong reported research funding from Dendreon.
At least one author on the second presentation reported employment and stock ownership with Dendreon.
Gomella reported relationships with Amgen, Caris MPI, Centocor Ortho Biotech, Dendreon, GlaxoSmithKline, sanofi-aventis, Watson Pharmaceuticals, and Photocure.