Sipuleucel-T, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer. It is a personalized treatment that works by programming each patient's immune system to seek out cancer and attack it as if it were foreign. While referred to as a therapeutic vaccine rather than a preventive vaccine that prevents infectious disease, sipuleucel-T is instead an immunostimulant.
Treatment method
A course of treatment consists of three basic steps:
The activated blood product is returned from the production facility to the infusion center and reinfused into the patient.
A complete sipuleucel-T treatment includes three courses at two week intervals.
Use
Sipuleucel-T is used to treat people with metastatic, asymptomatic, hormone-refractory prostate cancer. Other names for this stage are metastatic castrate-resistant and androgen independent or. This stage leads to mCRPC with lymph node involvement and distal tumors; this is the lethal stage of CaP. The prostate cancer staging designation is T4,N1,M1c.
Clinical trials
Completed
Sipuleucel-T showed overall survival benefit to patients in three double-blind randomized phase III clinical trials, D9901, D9902a, and IMPACT. The IMPACT trial served as the basis for FDA licensing. This trial enrolled 512 patients with asymptomatic or minimally symptomatic metastatic HRPC randomized in a 2:1 ratio. The median survival time for sipuleucel-T patients was 25.8 months comparing to 21.7 months for placebo-treated patients, an increase of 4.1 months. 31.7% of treated patients survived for 36 months vs. 23.0% in the control arm. Overall survival was statistically significant. The longer survival without tumor shrinkage or change in progression is surprising. This may suggest the effect of an unmeasured variable. The trial was conducted pursuant to a FDA Special Protocol Assessment, a set of guidelines binding trial investigators to specific agreed-upon parameters with respect to trial design, procedures and endpoints; compliance ensured overall scientific integrity and accelerated FDA approval. The D9901 trial enrolled 127 patients with asymptomatic metastatic HRPC randomized in a 2:1 ratio. The median survival time for patients treated with sipuleucel-T was 25.9 months comparing to 21.4 months for placebo-treated patients. Overall survival was statistically significant. The D9902a trial was designed like the D9901 trial but enrolled 98 patients. The median survival time for patients treated with sipuleucel-T was 19.0 months comparing to 15.3 months for placebo-treated patients, but did not reach statistical significance.
In progress
As of August 2014, the PRO Treatment and Early Cancer Treatment trial, a phase IIIB clinical trial started in 2001, was tracking subjects but no longer enrolling new subjects. Its purpose is to test efficacy for patients whose CaP is still controlled by either suppression of testosterone by hormone treatment or by surgical castration. Such patients have usually failed primary treatment of either surgical removal of the prostate,, internal radiation, BNCT or for curative intent. Such failure is called biochemical failure and is defined as a PSA reading of 2.0 ng/mL above nadir. As of August 2014, a clinical trial administering sipuleucel-T in conjunction with ipilimumab was tracking subjects but no longer enrolling new subjects; the trial evaluates the clinical safety and anti-cancer effects of the combination therapy in patients with advanced prostate cancer.
Side effects
Common side effects include: bladder pain; bloating or swelling of the face, arms, hands, lower legs, or feet; bloody or cloudy urine; body aches or pain; chest pain; chills; confusion; cough; diarrhea; difficult, burning, or painful urination; difficulty with breathing; difficulty with speaking up to inability to speak; double vision; sleeplessness; and inability to move the arms, legs, or facial muscles.
Regulatory approval and reimbursement
Sipuleucel-T was approved by the U.S. Food and Drug Administration on April 29, 2010, to treat asymptomatic or minimally symptomatic metastatic HRPC. Shortly afterward, sipuleucel-T was added to the compendium of cancer treatments published by the National Comprehensive Cancer Network as a "category 1" treatment for HRPC. The NCCN Compendium is used by Medicare and major health care insurance providers to decide whether a treatment should be reimbursed.
