Sipuleucel-T

{{Short description|Medication}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Use dmy dates|date=November 2025}} {{Infobox drug | image = | width = | alt = | caption =

| tradename = Provenge | Drugs.com = {{drugs.com|cons|sipuleucel-t-intravenous}} | MedlinePlus = a611025 | DailyMedID = Sipuleucel-T | pregnancy_AU =  | pregnancy_category = N/A (only approved in men, prostate cancer) | routes_of_administration = Intravenous | ATC_prefix = L03 | ATC_suffix = AX17 | ATC_supplemental =

| legal_AU =  | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Provenge FDA label">{{cite web | title = Provenge- sipuleucel-t injection | website = DailyMed | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8309b497-5d4e-4408-ac0c-2452c11c8a35 | access-date = 22 July 2021 }}</ref><ref name="FDA Provenge" /> | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

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'''Sipuleucel-T''', sold under the brand name '''Provenge''', developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP).<ref name="Provenge FDA label" /><ref name="Plosker_2011" /><ref name="US6210662" /> It is an autologous cellular immunotherapy.<ref name="Provenge FDA label" />

== Medical uses == 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.<ref name="Kantoff_2010" /><ref name="Small_2006" /><ref name="Longo_2010" />

=== Treatment method === 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.<ref name="Kantoff_2010" /><ref name="Small_2006" />

Premedication with acetaminophen and antihistamine is recommended to minimize side effects.<ref name="Kantoff_2010" />

==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.<ref name="MayoClinic1">{{cite web | title = Sipuleucel-T (Intravenous Route) - Side Effects | url = https://www.mayoclinic.org/drugs-supplements/sipuleucel-t-intravenous-route/side-effects/drg-20074285 | publisher = Mayo Clinic | access-date = 22 April 2015 }}</ref><ref name="FDA1">{{cite web | title = Package Insert and Patient Information - Provenge (PDF - 157KB) | 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 | publisher = U.S. Food and Drug Administration (FDA) | access-date = 22 April 2015 }}</ref>

== Society and culture == === Legal status === Sipuleucel-T was approved by the US Food and Drug Administration (FDA) in April 2010, to treat asymptomatic or minimally symptomatic metastatic HRPC.<ref name="Reuters approved"/><ref name= "FDA approval letter"/><ref name="FDA Provenge">{{cite web | title = Provenge (sipuleucel-T) | date = 22 July 2017 | website = U.S. Food and Drug Administration | 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 }}</ref><ref>{{cite web | title = Provenge (sipuleucel-T) | date = 14 July 2017 | website = U.S. Food and Drug Administration | 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 = 22 July 2017 | access-date = 1 April 2020 }}</ref><ref name="Provenge FDA label" />

Sipuleucel-T was added to the compendium of cancer treatments as a "category 1" (highest recommendation) treatment for HRPC.<ref name="provenge-nccn" /><ref name="about-nccn" /> The National Comprehensive Cancer Network (NCCN) Compendium is used by Medicare and major health care insurance providers to decide whether a treatment should be reimbursed.<ref name="provenge-nccn" /><ref name="about-nccn" />

== Research == ===Clinical trials===

==== Completed ==== Sipuleucel-T showed overall survival (OS) benefit to patients in three double-blind randomized phase III clinical trials, D9901,<ref name="Small_2006" /> D9902a,<ref name="Higano_2005" /><ref name="ECCO" /> and IMPACT.<ref name="Kantoff_2010" />

The IMPACT trial<ref name="Kantoff_2010" /> 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.<ref>{{cite book | vauthors = Lacroix M | title = Targeted Therapies in Cancer | location = Hauppauge, NY | date = 2014 | publisher = Nova Sciences Publishers | 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 }}</ref> 31.7% of treated patients survived for 36 months vs. 23.0% in the control arm.<ref name="Kantoff_2010" />

==== Ongoing ==== 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.<ref name="NCT00779402" /> 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).<ref name="Roach_2006" />

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.<ref name="sip-T-ipi-trial" />

Results from the large PROCEED registry, which enrolled men between 2011 and 2017, showed that men with metastatic castration-resistant prostate cancer had a median overall survival of approximately 30.7 months from the date of treatment, and that people with lower PSA levels had longer survival.<ref>{{Cite journal | vauthors = Higano C, Armstrong A, Sartor A, Vogelzang N, Kantoff P, McLeod D, Pieczonka C, Penson D, Shore N, Vacirca J, Concepcion R, Tutrone R, Nordquist L, Quinn D, Kassabian V | title = Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer | journal = Cancer | volume = 125 | issue = 23 | pages = 4172–4180 | year = 2019 | doi = 10.1002/cncr.32445 | pmid = 31483485 | pmc = 6856402 }}</ref> Research also found that African American men treated with Sipuleucel-T had similar or sometimes better survival than non-African American men, along with stronger immune activity, including higher levels of immune markers like ICOS, GM-CSF, CCL4 and CCL5.<ref>{{Cite journal | vauthors = Sartor O, Armstrong A, Ahaghotu C, McLeod D, Cooperberg M, Penson D, Kantoff P, Vogelzang N, Hussain A, Pieczonka C, Shore N, Quinn D, Small E, Heath E, Tutrone R | title = Survival of African-American and Caucasian men after Sipuleucel-T immunotherapy: Outcomes from the PROCEED registry | journal = Prostate Cancer and Prostatic Diseases | volume = 23 | issue = 3 | pages = 517–526 | date = Sep 2020 | doi = 10.1038/s41391-020-0213-7 | pmid = 32111923 | pmc = 7423504 }}</ref><ref name="Heath_2024">{{Cite journal | vauthors = Heath E, Thakur A, Chen W, Hwang C, Paller C, Cackowski F, Boerner J, Heilbrun L, Smith M, Schalk D, Schienschang A, Whitaker S, Polend A, Smith D, Vaishampayan U | title = Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate–Resistant Prostate Cancer | journal = Cancer Research Communications | volume = 4 | issue = 7 | pages = 1715–1725 | year = 2024 | doi = 10.1158/2767-9764.CRC-24-0112 | pmid = 38856749 | pmc = 11240276 }}</ref> These immune markers fit with the treatment's ability to stimulate antigen-presenting cells and downstream T-cell activity.<ref name="Heath_2024" />

== References == {{Reflist | refs =

<ref name="Plosker_2011">{{cite journal | vauthors = Plosker GL | title = Sipuleucel-T: in metastatic castration-resistant prostate cancer | journal = Drugs | volume = 71 | issue = 1 | pages = 101–108 | date = January 2011 | pmid = 21175243 | doi = 10.2165/11206840-000000000-00000 | s2cid = 209171318 }}</ref>

<ref name="US6210662">{{cite patent | country = US | number = 6210662| title = Immunostimulatory composition | inventor = Laus R, Ruegg CL, Wu H | assign = Dendreon Pharmaceuticals LLC | url = https://patents.google.com/patent/US6210662B1/en?oq=US6210662 }}</ref>

<ref name="Kantoff_2010">{{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 | title = Sipuleucel-T immunotherapy for castration-resistant prostate cancer | journal = The New England Journal of Medicine | volume = 363 | issue = 5 | pages = 411–422 | date = July 2010 | pmid = 20818862 | doi = 10.1056/NEJMoa1001294 | title-link = doi | doi-access = free }}</ref>

<ref name="Small_2006">{{cite journal | vauthors = Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM | 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 = 3089–3094 | date = July 2006 | pmid = 16809734 | doi = 10.1200/JCO.2005.04.5252 | title-link = doi | doi-access = free }}</ref>

<ref name="Longo_2010">{{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 = 479–481 | date = July 2010 | pmid = 20818868 | doi = 10.1056/NEJMe1006300 }}</ref>

<ref name="Reuters approved">{{cite news | vauthors = Richwine L | title = U.S. FDA OKs Dendreon's prostate cancer vaccine | date = 29 April 2010 | work = Reuters | url = https://www.reuters.com/article/idUSN2919838820100429 | access-date = 30 April 2010 }}</ref>

<ref name= "FDA approval letter">{{cite web | title = Approval Letter - Provenge | date = 29 April 2010 | 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 | publisher = Food and Drug Administration }}</ref>

<ref name="provenge-nccn">{{cite web | title = NCCN Guidelines and NCCN Compendium Updated | url = http://www.nccn.org/about/news/international_ebulletin/2010-07-26/guidelines_compendium.asp | access-date = 8 January 2011 | archive-url = https://web.archive.org/web/20120305083042/http://www.nccn.org/about/news/international_ebulletin/2010-07-26/guidelines_compendium.asp | archive-date = 5 March 2012 | work = National Comprehensive Cancer Network (NCCN) }}</ref>

<ref name="about-nccn">{{cite web | title = NCCN Drugs & Biologics Compendium | url = http://www.nccn.org/professionals/drug_compendium/content/contents.asp | archive-url = https://web.archive.org/web/20100703083549/http://www.nccn.org/professionals/drug_compendium/content/contents.asp | archive-date = 3 July 2010 | work = National Comprehensive Cancer Network (NCCN) }}</ref>

<ref name="Higano_2005">{{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 | location = Paris | date = October 2005 | conference = 13th European Cancer Conference }}</ref>

<ref name="ECCO">{{cite news | vauthors = K M | title = New treatment options for patients with prostate cancer | date = 2 November 2005 | url =https://www.eurekalert.org/news-releases/848464| agency = ECCO-the European CanCer Organisation }}</ref>

<ref name="Roach_2006">{{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 = 965–974 | date = July 2006 | pmid = 16798415 | doi = 10.1016/j.ijrobp.2006.04.029 }}</ref>

<ref name="NCT00779402">{{ClinicalTrialsGov|NCT00779402|Provenge Treatment and Early Cancer Treatment (PROTECT)}}</ref>

<ref name="sip-T-ipi-trial">{{cite journal | title = Sipuleucel-T and Ipilimumab for Advanced Prostate Cancer | journal = Clinicaltrials.gov | date = 23 August 2017 | url = https://clinicaltrials.gov/study/NCT01832870 | publisher = US National Institutes of Health }}</ref> }} {{NCI-cancer-dict}}

== Further reading == {{refbegin}} * {{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 = 273–279 | date = February 2012 | pmid = 22232132 | pmc = 3283534 | doi = 10.1093/jnci/djr514 }} * {{cite journal | 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 }} {{refend}}

Category:Cancer treatments Category:Prostate cancer Category:Cell therapies