The Dendreon Corportation announced that a dendritic cell vaccine, Provenge®, was associated with a median survival benefit of 4.5 months in a phase 3 study in advanced prostate cancer. This study will be presented later this month at the 2005 Multidisciplinary Prostate Cancer Symposium in California and at the 2005 meeting of the American Society of Clinical Oncology.
There are currently no FDA-approved vaccines for the treatment of cancer in the US. Vaccines usually consist of “tumor specific” antigens that stimulate the body to make immune cells that kill cancer cells. This sounds easy, but in fact it is difficult to identify and isolate tumor specific antigens and most efforts have been a failure. Another approach to vaccine development has been to use dendritic cells. Dendritic cells are antigen presenting cells that have been incorporated into several vaccine strategies over the past decade. Dendritic cells are CD34+ cells collected from the peripheral blood, usually after the administration of Neupogen®. Provenge® is a prototype dendritic vaccine that incorporates a specific antigen and a proprietary fusion protein of granulocyte-macrophage-colonly stimulating factor (GM-CSF), which are loaded onto autologous (from the patient) expanded antigen presenting cells (dendritic cells). The procedure requires mobilization and collection of peripheral blood stem cells (PBSC) for isolation of dendritic cells. Interestingly, this vaccine is given intravenously. Published phase I and II studies of Provenge® in patients with prostate cancer show that the vaccine is safe and may provide potential benefit.
A previous report of a phase III double-blind, randomized trial suggested that this vaccine might be effective in earlier stage prostate cancer. In that study, 82 patients were randomized to receive Provenge® and 45 were randomized to receive placebo. The endpoints were delay in pain and median time to tumor progression. There was no difference found in time to tumor progression between the two arms of this study. However, patients with Gleason scores lower than 7 had a decreased time to tumor progression compared to controls, but this was not observed in patients who had Gleason scores of 8 or more. The time to tumor progression was 9 weeks for the control group and 16 weeks for the vaccine group in those with low Gleason scores. A similar observation was made on time to pain development. Adverse events included fever and chills.
The current report from the Dendreon website describes a phase III study in 127 men with asymptomatic hormone-refractory metastatic prostate cancer who were randomized to receive three infusions of Provenge® or placebo over a four-week period. The analysis of this study was performed after a 36-month follow-up. The Dendreon website reported that “patients receiving Provenge® had a 4.5-month improvement in their average survival and a greater than 3-fold increase in survival at 36 months when compared to patients receiving placebo. Patients receiving Provenge ®had a median survival of 25.9 months compared to 21.4 months for patients in the placebo arm. In addition, 34% of patients receiving Provenge® were alive at 36 months, compared to 11% of patients receiving placebo. The survival benefit seen with Provenge® was independent of a patient’s Gleason Score. Provenge® was well tolerated with the most common adverse events reported being fever and chills lasting for one to two days”.
Dendreon is still enrolling patients on clinical trials and interested patients with advanced prostate cancer should discuss this option with their physician. Provenge® has Fast Track designation for FDA approval, which means that approval can be expedited. These are very good results for a vaccine of any type for the treatment of cancer; however, it will be important to review the final publication to determine the full impact of this study.
 Development of Therapeutic Cancer Vaccines conference held in Los Angeles, April 27-29, 2003. See conference coverage for 2003, cancerconsultants.com.
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