The cancer vaccine sipuleucel-T -- now commercially branded as Provenge -- will soon be available at a select group of medical centers nationwide, including UCSF.
Provenge is a newly-approved, life-extending prostate cancer treatment for men with advanced disease. Medical centers that helped to carry out the clinical trials leading to approval by the US Food and Drug Administration (FDA) will be the first to offer Provenge in standard practice. Within a few weeks, UCSF cancer specialists will become the first and only site in Northern California to make the treatment available to patients who are not participating in clinical trials.
At the end of April Provenge became the first cancer treatment vaccine to be approved by the FDA. Compared to chemotherapy, Provenge generally causes fewer and milder side effects.
UCSF medical researcher Eric Small, MD, has been involved in the development of the treatment. He conducted the first studies in patients, and has remained involved through the completion of advanced phase III clinical trials.
Small, a medical oncologist and the director of clinical sciences for the UCSF Helen Diller Family Comprehensive Cancer Center, is optimistic about the possibility that Provenge and other immunotherapies now in clinical trials will prove effective alone or in combination other drugs against all stages of prostate cancer.
“The stimulation of the immune system to attack cancer has been an elusive goal.The data that led to the FDA approval of Provenge is an important proof-of-concept.”
Production of Provenge Ramps Up
Provenge is expected to be in short supply for a year or two. Dendreon, the Seattle-based company that developed Provenge, is still ramping up its manufacturing capability. The company announced that treatment would initially become available at about 50 sites nationwide.
The FDA approved the use of Provenge to treat only certain men with prostate cancer. A man must have cancer that has spread to other tissues. He must be experiencing no symptoms, or only minor symptoms. He must be taking hormonal therapy to block the cancer-stimulating effects of testosterone. In addition, his PSA score must be rising over time, despite hormonal therapy. A rising PSA score is an indication that hormonal treatment may no longer be effective.
Provenge is made from a patient’s own immune cells. Certain immune cells are removed from the patient and trained to target a protein called PAP. PAP is found primarily on prostate tumor cells and on normal prostate cells. The patient receives three infusions of these immune cells, two weeks apart.
Compared to untargeted immune cells, Provenge extended patient survival by an average of four months in phase III clinical trials. Three times as many men treated with Provenge survived three years or more. Provenge does not appear to shrink tumors significantly. Nor does treatment cause a drop in PSA levels.
Provenge Studies for Early-stage Prostate Cancer at UCSF
Ongoing studies aim to evaluate Provenge treatment at earlier stages of prostate cancer. Researchers also are initiating studies to combine Provenge with other treatments.
At UCSF, urologic oncologist Lawrence Fong, MD, is leading a trial to evaluate Provenge treatment prior to surgery to remove the prostate. This trial is open only to men whose tumors have not spread beyond the prostate.
Clinical trials also are underway at UCSF to treat prostate cancer patients with other immunotherapies. UCSF physician-scientists are testing an immune-system-stimulating protein called GM-CSF. In one of these clinical trials, researchers are combining GM-CSF with an antibody.
The antibody, called ipilimumab, was developed by Medarex, now owned by Bristol-Myer-Squibb. The antibody targets a protein -- called CTLA-4 -- which acts like a set of brakes on the body’s immune system to prevent the body from attacking its own tissues.
Unfortunately, the immune system tolerates established tumors, which arise from normal tissue. By releasing the brakes, ipilimumab allows the immune system to attack tumors. Small led the first clinical trial of ipilimumab. The drug has not yet been approved for any use outside of clinical trials.