||This article needs to be updated. (December 2015)|
|Target disease||Prostate cancer|
|AHFS/Drugs.com||FDA Professional Drug Information|
|(what is this?)|
Sipuleucel-T (APC8015, trade name Provenge), developed by Dendreon Corporation, is a cell-based cancer immunotherapy for prostate cancer (CaP). 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.
On February 20, 2015, Valeant Pharmaceuticals received approval to purchase all Dendreon assets (including Provenge).
The treatment cost $93,000 at FDA approval, rising to over $100,000 in 2014.
A course of treatment consists of three basic steps:
- The patient's white blood cells, primarily dendritic cells, a type of antigen-presenting cells (APCs), 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 reinfused into the patient.
A complete sipuleucel-T treatment includes three courses at two week intervals.
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 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 (P=0.032). 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 (SPA), 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 (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.
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.
||This section needs to be updated. (December 2015)|
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.
- Plosker GL (January 2011). "Sipuleucel-T: in metastatic castration-resistant prostate cancer". Drugs. 71 (1): 101–8. PMID 21175243. doi:10.2165/11206840-000000000-00000.
- Immunostimulatory composition
- Exclusive: Questionable data propped up cancer drug Provenge, By Sharon Begley, Reuters, Oct 11, 2012
- Kantoff PW; Higano CS; Shore ND; Berger ER; Small EJ; Penson DF; Redfern CH; Ferrari AC; Dreicer R; Sims RB; Xu Y; Frohlich MW; Schellhammer PF (July 2010). "Sipuleucel-T immunotherapy for castration-resistant prostate cancer" (PDF). N. Engl. J. Med. 363 (5): 411–22. PMID 20818862. doi:10.1056/NEJMoa1001294.
- Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM (July 2006). "Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer" (PDF). J. Clin. Oncol. 24 (19): 3089–94. PMID 16809734. doi:10.1200/JCO.2005.04.5252.
- "Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine - Dendreon". Drugs R D. 7 (3): 197–201. 2006. PMID 16752945. doi:10.2165/00126839-200607030-00006.
- Longo DL (July 2010). "New therapies for castration-resistant prostate cancer". N. Engl. J. Med. 363 (5): 479–81. PMID 20818868. doi:10.1056/NEJMe1006300.
- Higano C, Burch P, Small E, Schellhammer P, Lemon R, Verjee S, Hershberg R (October 2005). Immunotherapy (APC8015) for androgen independent prostate cancer (AIPC): final progression and survival data from a second Phase 3 trial. 13th European Cancer Conference. Paris.
- Mason K (2005-11-02). "New treatment options for patients with prostate cancer". ECCO-the European CanCer Organisation.
- Lacroix, Marc (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7.
- Kantoff, Philip (July 29, 2010). "Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer". The New England Journal of Medicine. 363 (5): 411–22. PMID 20818862. doi:10.1056/NEJMoa1001294.
- "NCT00779402: Provenge for the Treatment of Hormone Sensitive Prostate Cancer". ClinicalTrials.gov. US National Institutes of Health.
- Roach M; Hanks G; Thames H; Schellhammer P; Shipley WU; Sokol GH; Sandler H (July 2006). "Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference". Int. J. Radiat. Oncol. Biol. Phys. 65 (4): 965–74. PMID 16798415. doi:10.1016/j.ijrobp.2006.04.029.
- "Sipuleucel-T and ipilimumab clinical trials". ClinicalTrials.gov. US National Institutes of Health.
- "Sipuleucel-T (Intravenous Route) - Side Effects". Mayo Clinic. Retrieved 22 April 2015.
- "Package Insert and Patient Information - Provenge (PDF - 157KB)" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 22 April 2015.
- Richwine L (2010-04-29). "U.S. FDA OKs Dendreon's prostate cancer vaccine". Reuters. Retrieved 2010-04-30.
- "Approval Letter - Provenge". Food and Drug Administration. 2010-04-29.
- "NCCN Guidelines and NCCN Compendium Updated". Retrieved 2011-01-08.
- "NCCN Drugs & Biologics Compendium".
- Official website
- "Provenge (sipuleucel-T)". FDA Vaccines, Blood & Biologics.
- "Provenge Package Insert and Patient Information". FDA.
- "Provenge". Daily Med.