Benefits for men with metastatic hormone-refractory prostate cancer.


SAN DIEGO—Dutch researchers have reported preliminary success with a combination of the GVAX immunotherapeutic vaccine and ipilimumab (MDX-010, Medarex, Inc) in patients with metastatic hormone-refractory prostate cancer. 

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The two therapies, which have a promising synergistic effect, helped lower PSA levels in some patients.


“Higher doses of ipilimumab combined with the GVAX vaccine is showing a lot of success in increasing anti-tumor activity in these patients,” said Saskia Santegoets, PhD, a researcher in the department of pathology and division of immunotherapy at the Vrije Universiteit Medical Center in Amsterdam.


“We’re encouraged by the results of this phase I trial and expect ongoing analyses to yield more valuable data about the GVAX/ipilimumab combination.”


In this phase I trial, the vaccine was administered with escalating doses of ipilimumab. The researchers believe that the combination of these two immunotherapies increases one’s immunity to prostate cancer. It is thought the two drugs together augment T-cell mediated anti-tumor immunity via improved dendritic cell (DC) functions and blockade of inhibitory feedback loops in activated tumor-specific T cells.


A total of 12 patients were enrolled in the study and all were given the same doses of GVAX (a 500 million-cell first dose followed by biweekly 300 million-cell doses for 24 weeks). In groups of three, different quantities of ipilimumab were administered every four weeks (0.3, 1, 3, or 5 mg).


In five of the six patients receiving the two highest doses of ipilimumab, the investigators observed anti-tumor activity and PSA declines of greater than 50%. Of these five patients, two had resolution of multiple lesions as shown on bone scans, one had resolution of abdominial lymph node disease demonstrated on CT scans, and one patient had improvement in bone pain.


PSA declines were maintained in four of the five patients for at least six months and for as long as 16 months. Pre-treatment frequencies of circulating myeloid DC subsets were significantly reduced in the patients receiving this combination therapy compared to age-matched and sex-matched healthy controls. “We saw some side effects but they were all manageable with hormone replacement therapy,” Dr. Santegoets said.


Findings were reported here at the American Association for Cancer Research annual meeting.