Sipuleucel-T
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| Trade names | Provenge |
| Other names | APC8015 |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| MedlinePlus | a611025 |
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| Routes of administration | Intravenous |
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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).[1][3][4] It is an autologous cellular immunotherapy.[1]
Medical uses
[edit]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.[5][6][7]
Treatment method
[edit]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.[5][6]
Premedication with acetaminophen and antihistamine is recommended to minimize side effects.[5]
Side effects
[edit]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.[8][9]
Society and culture
[edit]Legal status
[edit]Sipuleucel-T was approved by the US Food and Drug Administration (FDA) in April 2010, to treat asymptomatic or minimally symptomatic metastatic HRPC.[10][11][2][12][1]
Sipuleucel-T was added to the compendium of cancer treatments as a "category 1" (highest recommendation) treatment for HRPC.[13][14] 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.[13][14]
Research
[edit]Clinical trials
[edit]Completed
[edit]Sipuleucel-T showed overall survival (OS) benefit to patients in three double-blind randomized phase III clinical trials, D9901,[6] D9902a,[15][16] and IMPACT.[5]
The IMPACT trial[5] 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.[17] 31.7% of treated patients survived for 36 months vs. 23.0% in the control arm.[5]
Ongoing
[edit]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.[18] 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).[19]
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.[20]
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.[21] 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.[22][23] These immune markers fit with the treatment’s ability to stimulate antigen-presenting cells and downstream T-cell activity.[23]
References
[edit]- ^ a b c d "Provenge- sipuleucel-t injection". DailyMed. Retrieved 22 July 2021.
- ^ a b "Provenge (sipuleucel-T)". U.S. Food and Drug Administration. 22 July 2017. Archived from the original on 30 August 2019. Retrieved 1 April 2020.
- ^ Plosker GL (January 2011). "Sipuleucel-T: in metastatic castration-resistant prostate cancer". Drugs. 71 (1): 101–108. doi:10.2165/11206840-000000000-00000. PMID 21175243. S2CID 209171318.
- ^ US 6210662, Laus R, Ruegg CL, Wu H, "Immunostimulatory composition", assigned to Dendreon Pharmaceuticals LLC
- ^ a b c d e f Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. (July 2010). "Sipuleucel-T immunotherapy for castration-resistant prostate cancer". The New England Journal of Medicine. 363 (5): 411–422. doi:10.1056/NEJMoa1001294. PMID 20818862.
- ^ a b c Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, et al. (July 2006). "Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer". Journal of Clinical Oncology. 24 (19): 3089–3094. doi:10.1200/JCO.2005.04.5252. PMID 16809734.
- ^ Longo DL (July 2010). "New therapies for castration-resistant prostate cancer". The New England Journal of Medicine. 363 (5): 479–481. doi:10.1056/NEJMe1006300. PMID 20818868.
- ^ "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). Archived from the original (PDF) on 1 June 2010. Retrieved 22 April 2015.
- ^ Richwine L (29 April 2010). "U.S. FDA OKs Dendreon's prostate cancer vaccine". Reuters. Retrieved 30 April 2010.
- ^ "Approval Letter - Provenge". Food and Drug Administration. 29 April 2010. Archived from the original on 6 May 2010.
- ^ "Provenge (sipuleucel-T)". U.S. Food and Drug Administration. 14 July 2017. Archived from the original on 22 July 2017. Retrieved 1 April 2020.
- ^ a b "NCCN Guidelines and NCCN Compendium Updated". National Comprehensive Cancer Network (NCCN). Archived from the original on 5 March 2012. Retrieved 8 January 2011.
- ^ a b "NCCN Drugs & Biologics Compendium". National Comprehensive Cancer Network (NCCN). Archived from the original on 3 July 2010.
- ^ Higano C, Burch P, Small E, Schellhammer P, Lemon R, Verjee S, et al. (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.
- ^ K M (2 November 2005). "New treatment options for patients with prostate cancer". ECCO-the European CanCer Organisation.
- ^ Lacroix M (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. Archived from the original on 26 June 2015. Retrieved 20 July 2014.
- ^ Clinical trial number NCT00779402 for "Provenge Treatment and Early Cancer Treatment (PROTECT)" at ClinicalTrials.gov
- ^ Roach M, Hanks G, Thames H, Schellhammer P, Shipley WU, Sokol GH, et al. (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". International Journal of Radiation Oncology, Biology, Physics. 65 (4): 965–974. doi:10.1016/j.ijrobp.2006.04.029. PMID 16798415.
- ^ "Sipuleucel-T and Ipilimumab for Advanced Prostate Cancer". Clinicaltrials.gov. US National Institutes of Health. 23 August 2017.
- ^ Higano C, Armstrong A, Sartor A, Vogelzang N, Kantoff P, McLeod D, et al. (2019). "Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer". Cancer. 125 (23): 4172–4180. doi:10.1002/cncr.32445. PMC 6856402. PMID 31483485.
- ^ Sartor O, Armstrong A, Ahaghotu C, McLeod D, Cooperberg M, Penson D, et al. (September 2020). "Survival of African-American and Caucasian men after Sipuleucel-T immunotherapy: Outcomes from the PROCEED registry". Prostate Cancer and Prostatic Diseases. 23 (3): 517–526. doi:10.1038/s41391-020-0213-7. PMC 7423504. PMID 32111923.
- ^ a b Heath E, Thakur A, Chen W, Hwang C, Paller C, Cackowski F, et al. (2024). "Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate–Resistant Prostate Cancer". Cancer Research Communications. 4 (7): 1715–1725. doi:10.1158/2767-9764.CRC-24-0112. PMC 11240276. PMID 38856749.
This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.
Further reading
[edit]- Huber ML, Haynes L, Parker C, Iversen P (February 2012). "Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer". Journal of the National Cancer Institute. 104 (4): 273–279. doi:10.1093/jnci/djr514. PMC 3283534. PMID 22232132.
- "Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon". Drugs in R&D. 7 (3): 197–201. 2006. doi:10.2165/00126839-200607030-00006. PMID 16752945. S2CID 6427074.
