Vaccine for hormone-refractory prostate cancer is well tolerated

Atlanta-An investigational vaccine directed against prostate cancer cells has been found to be well tolerated with minimal toxicity in patients with hormone-refractory prostate cancer. In patients receiving the agent, median survival appeared to be enhanced when compared with accepted nomograms, reported researchers from Virginia Mason Medical Center, Seattle. These results were from two phase II trials of the vaccine, known as GVAX, presented at the AUA annual meeting here.

"For patients who have advanced disease that is hormone refractory, this is a novel technique of harnessing the immune system that appears to be safe and well tolerated. Phase III studies are underway to assess survival benefits with GVAX as opposed to standard cytotoxic therapy," lead author John Corman, MD, co-director of urologic oncology at Virginia Mason, told Urology Times.

The vaccine is composed of two irradiated prostate carcinoma cell lines, PC-3 and LNCap, which are genetically engineered to secrete granulocyte macrophage-colony stimulating factor (GM-CSF) in order to elicit an immune response against prostate cancer. The vaccine was administered intradermally every 2 weeks for 24 weeks or until disease progression.

"With this vaccine, we are providing patients with cytokine and multiple antigens. The antigens have been derived from prostate cancer cell lines. The patient himself ultimately provides his own antigen-presenting cells and effector cells, T-cells," Dr. Corman explained.

Patients chosen for these studies had metastatic hormone-refractory prostate cancer and no prior chemotherapy. The vast majority had Gleason scores of >5 and no evidence of visceral disease. Median age of patients was 72 years in study G-9803 and 69 years in G-0010, with a range of 49 to 90 years. In both studies, 82% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

PSA stabilized or decreased

Overall survival was measured and compared with predicted survival for these patients in the absence of treatment. Predicted survival was calculated using a validated prognostic method developed by Susan Halabi, MD, which uses various patient characteristics to predict outcome in hormone-refractory disease (J Clin Oncol 2003; 21:1232-7). The characteristics used to predict outcome were PSA, alkaline phosphatase, hemoglobin, lactate dehydrogenase, Gleason score, ECOG performance status, and presence/absence of visceral disease.

GVAX improved overall survival in both phase II studies. In G-9803, median survival was 26.2 months for treated patients compared with a predicted survival of 19.5 months for these patients if untreated. In G-0010, median survival for vaccine patients has not yet been reached, but is expected to be at least 29.1 months, versus a predicted survival of 22 months for untreated patients.

GVAX use was also associated with stabilized or decreased PSA levels and levels of type I carboxyterminal telopeptide, a marker of osteolytic activity.

Side effects of GVAX were mild to moderate. The most frequent was injection site reaction followed by development of flu-like symptoms.

"I've had no one withdraw because of side effects; [the vaccine was] generally very well tolerated," Dr. Corman said.

Two phase III studies of GVAX are currently underway. The first is for asymptomatic patients with metastatic hormone-refractory disease who will be randomized to either vaccine or standard docetaxel (Taxotere)/prednisone chemotherapy. The second is for metastatic hormone-refractory patients with bone pain. These patients will be randomized to either vaccine plus docetaxel or docetaxel/prednisone alone. Both trials will recruit approximately 600 patients with survival as the primary endpoint.

This study was sponsored by Cell Genesys, Inc., maker of the vaccine.