Sipuleucel-T

Sipuleucel-T is indicated for the treatment of metastatic, asymptomatic or minimally symptomatic, metastatic castrate-resistant 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.

File:Sipuleucel-T.png]]

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 antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cells and
• An immune signaling factor granulocyte-macrophage colony stimulating factor (GM-CSF) that helps the APCs to mature.
• The activated blood product (APC8015) is returned from the production facility to the infusion center and reinfused into the patient.

Premedication with acetaminophen and antihistamine is recommended to minimize side effects.{{cite journal | vauthors = 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 | display-authors = 6 | title = Sipuleucel-T immunotherapy for castration-resistant prostate cancer | journal = The New England Journal of Medicine | volume = 363 | issue = 5 | pages = 411–22 | date = July 2010 | pmid = 20818862 | doi = 10.1056/NEJMoa1001294 | doi-access = free }}

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.{{cite web|url=https://www.mayoclinic.org/drugs-supplements/sipuleucel-t-intravenous-route/side-effects/drg-20074285|title=Sipuleucel-T (Intravenous Route) - Side Effects |publisher=Mayo Clinic|access-date=22 April 2015}}{{cite web|url=https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM210031.pdf|archive-url=https://web.archive.org/web/20100601204657/http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM210031.pdf|url-status=dead|archive-date=1 June 2010|title=Package Insert and Patient Information - Provenge (PDF - 157KB)|publisher=U.S. Food and Drug Administration (FDA)|access-date=22 April 2015}}

Sipuleucel-T was approved by the U.S. Food and Drug Administration (FDA) on April 29, 2010, to treat asymptomatic or minimally symptomatic metastatic HRPC.{{cite web | title=Provenge (sipuleucel-T) | website=U.S. Food and Drug Administration | date=22 July 2017 | url=https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/provenge-sipuleucel-t | archive-url=https://web.archive.org/web/20190830204607/https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/provenge-sipuleucel-t | url-status=dead | archive-date=30 August 2019 | access-date=1 April 2020}}{{cite web | title=Provenge (sipuleucel-T) | website=U.S. Food and Drug Administration | date=14 July 2017 | url=https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210012.htm | archive-url=https://wayback.archive-it.org/7993/20170722071307/https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210012.htm | url-status=unfit | archive-date=2017-07-22 | access-date=1 April 2020}}

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.

Sipuleucel-T showed overall survival (OS) 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.{{cite book|vauthors=Lacroix M|title=Targeted Therapies in Cancer|date=2014|publisher=Nova Sciences Publishers|location=Hauppauge, NY|isbn=978-1-63321-687-7|url=https://www.novapublishers.com/catalog/product_info.php?products_id=50994|access-date=20 July 2014|archive-date=26 June 2015|archive-url=https://web.archive.org/web/20150626172243/https://www.novapublishers.com/catalog/product_info.php?products_id=50994|url-status=dead}} 31.7% of treated patients survived for 36 months vs. 23.0% in the control arm.{{cite journal | vauthors = 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 | display-authors = 6 | title = Sipuleucel-T immunotherapy for castration-resistant prostate cancer | journal = The New England Journal of Medicine | volume = 363 | issue = 5 | pages = 411–22 | date = July 2010 | pmid = 20818862 | doi = 10.1056/NEJMoa1001294 | doi-access = free }} 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.{{citation needed|date=April 2015}}

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).{{cn|date=May 2021}}

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.{{cn|date=May 2021}}

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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{{cite journal | vauthors = Plosker GL | title = Sipuleucel-T: in metastatic castration-resistant prostate cancer | journal = Drugs | volume = 71 | issue = 1 | pages = 101–8 | date = January 2011 | pmid = 21175243 | doi = 10.2165/11206840-000000000-00000 | s2cid = 209171318 }}

{{US patent|6210662|Immunostimulatory composition}}

{{cite journal | vauthors = 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 | display-authors = 6 | title = Sipuleucel-T immunotherapy for castration-resistant prostate cancer | journal = The New England Journal of Medicine | volume = 363 | issue = 5 | pages = 411–22 | date = July 2010 | pmid = 20818862 | doi = 10.1056/NEJMoa1001294 | doi-access = free }}

{{cite journal | vauthors = Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM | display-authors = 6 | title = Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer | journal = Journal of Clinical Oncology | volume = 24 | issue = 19 | pages = 3089–94 | date = July 2006 | pmid = 16809734 | doi = 10.1200/JCO.2005.04.5252 | doi-access = free }}

{{cite journal | vauthors = Longo DL | title = New therapies for castration-resistant prostate cancer | journal = The New England Journal of Medicine | volume = 363 | issue = 5 | pages = 479–81 | date = July 2010 | pmid = 20818868 | doi = 10.1056/NEJMe1006300 }}

{{cite news | title=U.S. FDA OKs Dendreon's prostate cancer vaccine | author = Richwine L | work = Reuters| date = 2010-04-29 | url = https://www.reuters.com/article/idUSN2919838820100429 | access-date = 2010-04-30 }}

{{cite web |url=https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210215.htm |archive-url=https://web.archive.org/web/20100506034806/http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210215.htm |url-status=dead |archive-date=6 May 2010 | title=Approval Letter - Provenge | publisher=Food and Drug Administration | date=2010-04-29 }}

{{cite web | url = http://www.nccn.org/about/news/international_ebulletin/2010-07-26/guidelines_compendium.asp | title = NCCN Guidelines and NCCN Compendium Updated | access-date = 2011-01-08}}

{{cite web | url = http://www.nccn.org/professionals/drug_compendium/content/contents.asp | title = NCCN Drugs & Biologics Compendium }}

{{cite conference |vauthors=Higano C, Burch P, Small E, Schellhammer P, Lemon R, Verjee S, Hershberg R | title = Immunotherapy (APC8015) for androgen independent prostate cancer (AIPC): final progression and survival data from a second Phase 3 trial | conference = 13th European Cancer Conference | location = Paris |date=October 2005 }}

{{cite news | url = http://www.eurekalert.org/pub_releases/2005-11/foec-nto110205.php | author = Mason K | agency = ECCO-the European CanCer Organisation | date = 2005-11-02 | title = New treatment options for patients with prostate cancer}}

{{cite journal | vauthors = Roach M, Hanks G, Thames H, Schellhammer P, Shipley WU, Sokol GH, Sandler H | title = 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 | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 65 | issue = 4 | pages = 965–74 | date = July 2006 | pmid = 16798415 | doi = 10.1016/j.ijrobp.2006.04.029 }}

{{cite journal | url = http://clinicaltrials.gov/ct2/show/NCT00779402 | title = NCT00779402: Provenge for the Treatment of Hormone Sensitive Prostate Cancer | journal = ClinicalTrials.gov | date = 29 June 2017 | publisher = US National Institutes of Health }}

{{cite journal | url=http://clinicaltrials.gov/ct2/show/NCT01832870?term=sipipi&rank=1 | title=Sipuleucel-T and ipilimumab clinical trials | journal = ClinicalTrials.gov | date=23 August 2017 | publisher = US National Institutes of Health}}

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{{NCI-cancer-dict}}

• {{cite journal | vauthors=Huber ML, Haynes L, Parker C, Iversen P | title = Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer | journal = Journal of the National Cancer Institute | volume = 104 | issue = 4 | pages = 273–9 |date=February 2012 | doi = 10.1093/jnci/djr514 | pmid = 22232132 | pmc = 3283534 }}
• {{cite journal | vauthors = | title = Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon | journal = Drugs in R&D | volume = 7 | issue = 3 | pages = 197–201 | year = 2006 | pmid = 16752945 | doi = 10.2165/00126839-200607030-00006 | s2cid = 6427074 }}

• {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/sipuleucel-t | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Sipuleucel-T }}

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Category:Cancer treatments

Category:Prostate cancer

Category:Cell therapies