|Target disease||Prostate cancer|
|(what is this?)|
Sipuleucel-T (APC8015, trade name Provenge), manufactured by Dendreon Corporation, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is a personalized treatment that works by programming a patient's own immune system to seek out cancer spreading in the body, and attack it as if it were foreign. It must be prepared specifically for each patient. In metastatic prostate cancer, it has extended survival by median 4.1 months (IMPACT Phase III trial data). Improvements in 3-year survival rates have also been shown, with 31.7% of treated patients surviving for 36 months vs. 23.0% in the control arm. The treatment cost $93,000 at FDA approval, but rose to over $100,000 in 2014. This compares to an average cost of $175,000, for a typical course of treatment in cancer or other life threatening disease. 
A course of sipuleucel-T treatment consists of three basic steps:
- A patient's own white blood cells, primarily antigen-presenting cells (APCs), also called dendritic cells, are extracted in a leukapheresis procedure.
- The blood product is sent to a production facility and incubated with a fusion protein (PA2024) consisting of two parts,
- The activated blood product (APC8015) is returned from the production facility to the infusion center and re-infused into the patient to cause an immune response against cancer cells carrying the PAP antigen.
A complete sipuleucel-T treatment repeats three courses, with two weeks between successive courses.
Sipuleucel-T is used to treat people with metastatic, asymptomatic, hormone-refractory prostate cancer (HRPC). Other names for this stage are metastatic castrate-resistant (mCRPC) and androgen independent (AI) or (AIPC). This stage leads to mCRPC with lymph node involvement and distal (distant) tumors; this is the lethal stage of CaP. The prostate cancer staging designation is T4,N1,M1c.
The IMPACT trial served as the basis for licensing approval of sipuleucel-T by the FDA. 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. Overall survival was statistically significant (P=0.032). However, a better control group would have included patients receiving white blood cells incubated with GM-CSF alone, so that the main difference between the two groups would have been the tumor antigen. Furthermore, the longer survival without tumor shrinkage or change in progression is surprising. This may suggest the effect of an unmeasured variable. Nevertheless, the IMPACT trial was conducted pursuant to a FDA Special Protocol Assessment (SPA), a set of guidelines binding trial investigators to specific agreed-upon parameters with respect to trial design, procedures, and endpoints measured; trial regulatory value as the basis for FDA approval as well as overall scientific integrity were thus prioritized and ensured via such compliance.
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 (P=0.01).
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.
The most 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; sleeplessnes; and inability to move the arms, legs, or facial muscles.
Regulatory approval and reimbursement
Shortly afterward, sipuleucel-T was added to the compendium of cancer treatments published by the National Comprehensive Cancer Network (NCCN) as a "category 1" (highest recommendation) treatment for HRPC. The NCCN Compendium is used by Medicare and major health care insurance providers to decide whether a treatment should be reimbursed.
As of August 2014, the PRO Treatment and Early Cancer Treatment (PROTECT) 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, (EBRT), internal radiation, BNCT or (HIFU) for curative intent. Such failure is called biochemical failure and is defined as a PSA reading of 2.0 ng/mL above nadir (the lowest reading taken post primary treatment).
As of August 2014, a clinical trial administering sipuleucel-T in conjunction with ipilimumab (Yervoy) was tracking subjects but no longer enrolling new subjects; the trial evaluates the clinical safety and anti-cancer effects (quantified in PSA, radiographic, and T cell response) of the combination therapy in patients with advanced prostate cancer.
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