Prostate Cancer Cell Line Vaccine Promising in Phase II Trial

ORLANDO—In patients with hormone-refractory, metastatic prostate cancer, an allogeneic vaccine delays progression of disease and prolongs survival, according to data presented at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 729).

In this phase II study of 34 patients, the vaccine (GVAX, Cell Genesys, Inc., Foster City, California) showed evidence of a dose-response relationship in prostate-specific antigen (PSA) progression, time to progression, and survival, setting the stage for a phase III trial scheduled to be launched in the first half of 2003.

"The more important work is up ahead," said lead investigator Jon-athan Simons, MD, director, Winship Cancer Institute, Atlanta. "Now that a safe range of doses has been defined, larger clinical trials can be done."

The vaccine is composed of PC-3 and LNCaP tumor cells irradiated and genetically modified to secrete granulocyte macophage colony-simulating factor (GM-CSF).

In this study, there were no dose-limiting or autoimmune toxicities in 24 patients given a lower vaccine dose (prime dose of 500 million cells, followed by 12 booster doses of 100 million cells each) or in 10 patients given a higher dose (same prime dose, but with booster doses of 300 million cells each).

Toxicities primarily consisted of nonserious injection site reactions, along with fatigue, fever, and flu-like symptoms.

Trend Toward Increased Survival

There was a trend toward increased overall survival in the higher-dose group. Of 22 patients in the low-dose group (2 lost to follow-up), 9 patients (41%) were alive at 2-year follow-up, compared with 7 of 10 patients (70%) in the higher-dose group. There was also a trend toward longer median time to disease progression (measured by bone scan) for the patients who received the high-dose regimen (140 days vs 85 days).

Antitumor activity included one complete response by PSA determination. "Prior to the trial, no one believed that immunotherapy could induce complete responses in an area where traditional chemotherapy has been used," said Dale Ando, MD, vice president of Cell Genesys, Inc., the company developing the vaccine product.

Newer, More Potent Version

While the vaccine approach clearly merits further study in hormone-refractory disease, there are still outstanding questions, including cost and combinations with chemotherapy. Perhaps the most important question, though, is what vaccine composition is best to move forward, particularly now that Dr. Simons and his colleagues have a more potent vaccine to study.

Phase I/II trials are planned of the newer vaccine variant, which secretes GM-CSF at levels 5 to 10 times higher than the vaccine reported at ASCO. The newer vaccine will be studied in patients with hormone-refractory prostate cancer and metastatic bone disease.

Discussant Michael A. Carducci, MD, co-director of the Drug Development Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, commented: "The field of immunotherapy vaccines is hindered by the fact that we don’t know what the best product is. If vaccines are going to be evaluated like other, more traditional drugs, at some point you have to commit to a product and test it."

The upcoming phase III trial of GVAX will likely pit vaccine against standard-of-care cytotoxic drugs for hormone-
refractory prostate cancer, Dr. Simons said.