Sipuleucel-T

Last updated

Sipuleucel-T
Clinical data
Trade names Provenge
Other namesAPC8015
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a611025
License data
Pregnancy
category
  • N/A (only approved in men, prostate cancer)
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • None
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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]

Contents

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. [5] [6] [7]

Treatment method

A course of treatment consists of three basic steps:

Premedication with acetaminophen and antihistamine is recommended to minimize side effects. [8]

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. [9] [10]

Society and culture

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. [11] [12] [2] [13] [1]

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. [14] [15]

Research

Clinical trials

Completed

Sipuleucel-T showed overall survival (OS) benefit to patients in three double-blind randomized phase III clinical trials, D9901, [6] D9902a, [16] [17] 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. [18] 31.7% of treated patients survived for 36 months vs. 23.0% in the control arm. [19] 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. [7] 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 ]

The D9901 trial [6] 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).[ citation needed ]

The D9902a trial [16] 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.[ citation needed ]

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. [20] 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). [21]

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. [22]

Related Research Articles

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

Nicholas J. Vogelzang was a medical oncologist with Comprehensive Cancer Centers of Nevada (CCCN). He serves as medical director of the Research Executive Committee and Associate Chair of the Developmental Therapeutics and Genitourinary Committees for US Oncology Research. His research interests include clinical trials for genitourinary malignancies and mesothelioma.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">Enzalutamide</span> Antiandrogen medication used in treatment of prostate cancer

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

Radium-223 is an isotope of radium with an 11.4-day half-life. It was discovered in 1905 by T. Godlewski, a Polish chemist from Kraków, and was historically known as actinium X (AcX). Radium-223 dichloride is an alpha particle-emitting radiotherapy drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover. The principal use of radium-223, as a radiopharmaceutical to treat metastatic cancers in bone, takes advantage of its chemical similarity to calcium, and the short range of the alpha radiation it emits.

James L. Gulley is an American cancer researcher and the Director of the Medical Oncology Service at National Cancer Institute.

Simon J. Hall is an American researcher who is the Associate Professor and Kyung Hyun Kim, M.D. Chair of Urology and Assistant Professor, Department of Gene and Cell Medicine at The Mount Sinai School of Medicine, as well as the Director of the Barbara and Maurice Deane Prostate Health and Research Center at The Mount Sinai Medical Center, both in New York City.

Dendreon is a biotechnology company. Its lead product, Provenge, is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells that have been incubated with the Dendreon PAP-GM-CSF fusion protein. Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009. After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010. Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge.

<span class="mw-page-title-main">Cabazitaxel</span> Chemical compound

Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

<span class="mw-page-title-main">Tasquinimod</span> Chemical compound

Tasquinimod is an experimental drug currently being investigated for the treatment of solid tumors. Tasquinimod has been mostly studied in prostate cancer, but its mechanism of action suggests that it could be used to treat other cancers. Castration-resistant prostate cancer (CRPC), formerly called hormone-resistant or hormone-refractory prostate cancer, is prostate cancer that grows despite medical or surgical androgen deprivation therapy. Tasquinimod targets the tumor microenvironment and counteracts cancer development by inhibiting angiogenesis and metastasis and by modulating the immune system. It is now in phase III development, following successful phase II trial outcomes.

PROSTVAC is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of all prostate cancer although clinical trials are focusing on more advanced cases of metastatic castration-resistant prostate cancer (mCRPC). PROSTVAC is a vaccine designed to enable the immune system to recognize and attack prostate cancer cells by triggering a specific and targeted T cell immune response to cancer cells that express the tumor-associated antigen prostate-specific antigen (PSA).

Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men. It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration. The medication is taken by mouth twice per day with food.

<span class="mw-page-title-main">Apalutamide</span> Chemical compound

Apalutamide, sold under the brand name Erleada among others, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC). It is taken by mouth.

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

The Immune Response Corporation (IRC) was a pharmaceutical company that worked in the development immunotherapeutic products. The firm was founded by Jonas Salk and Kevin Kimberlin when Kimberlin, "asked Salk to become lead scientific advisor for a new biotech company specializing in 'anti-idiotypes,' a novel vaccine technology." Salk called the proposal "liberating."

A therapeutic vaccine is a vaccine which is administered after a disease or infection has already occurred. A therapeutic vaccine works by activating the immune system of a patient to fight an infection. A therapeutic vaccine differs from a prophylactic vaccine in that prophylactic vaccines are administered to individuals as a precautionary measure to avoid the infection or disease while therapeutic vaccines are administered after the individual is already affected by the disease or infection. A therapeutic vaccine fights an existing infection in the body rather than immunizing the body for protection against future diseases and infections. Therapeutic vaccines are mostly used against viral infections. Patients affected with chronic viral infections are administered with therapeutic vaccines, as their immune system is not able to produce enough efficient antibodies.

<span class="mw-page-title-main">Philip Kantoff</span> Medical researcher

Philip W. Kantoff is a medical oncologist. He is the chairman and chief executive officer (CEO) of Convergent Therapeutics. He served as the Chairman of Medicine at Memorial Sloan Kettering Cancer Center between 2015 and 2021. He is best known for his contributions to the impact of DNA abnormalities in prostate cancer and the discovery of therapies for metastatic hormone-sensitive prostate cancer.

References

  1. 1 2 3 4 "Provenge- sipuleucel-t injection". DailyMed. Retrieved 22 July 2021.
  2. 1 2 "Provenge (sipuleucel-T)". U.S. Food and Drug Administration. 22 July 2017. Retrieved 1 April 2020.
  3. ↑ Plosker GL (January 2011). "Sipuleucel-T: in metastatic castration-resistant prostate cancer". Drugs. 71 (1): 101–8. doi:10.2165/11206840-000000000-00000. PMID   21175243. S2CID   209171318.
  4. ↑ Immunostimulatory composition
  5. 1 2 3 4 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): 411–22. doi: 10.1056/NEJMoa1001294 . PMID   20818862.
  6. 1 2 3 4 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): 3089–94. doi: 10.1200/JCO.2005.04.5252 . PMID   16809734.
  7. 1 2 Longo DL (July 2010). "New therapies for castration-resistant prostate cancer". The New England Journal of Medicine. 363 (5): 479–81. doi:10.1056/NEJMe1006300. PMID   20818868.
  8. ↑ 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): 411–22. doi: 10.1056/NEJMoa1001294 . PMID   20818862.
  9. ↑ "Sipuleucel-T (Intravenous Route) - Side Effects". Mayo Clinic. Retrieved 22 April 2015.
  10. ↑ "Package Insert and Patient Information - Provenge (PDF - 157KB)" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 22 April 2015.
  11. ↑ Richwine L (29 April 2010). "U.S. FDA OKs Dendreon's prostate cancer vaccine". Reuters. Retrieved 30 April 2010.
  12. ↑ "Approval Letter - Provenge". Food and Drug Administration. 29 April 2010.
  13. ↑ "Provenge (sipuleucel-T)". U.S. Food and Drug Administration. 14 July 2017. Archived from the original on 22 July 2017. Retrieved 1 April 2020.{{cite web}}: CS1 maint: unfit URL (link)
  14. ↑ "NCCN Guidelines and NCCN Compendium Updated" . Retrieved 8 January 2011.
  15. ↑ "NCCN Drugs & Biologics Compendium".
  16. 1 2 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.
  17. ↑ Mason K (2 November 2005). "New treatment options for patients with prostate cancer". ECCO-the European CanCer Organisation.
  18. ↑ 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.
  19. ↑ 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): 411–22. doi: 10.1056/NEJMoa1001294 . PMID   20818862.
  20. ↑ "NCT00779402: Provenge for the Treatment of Hormone Sensitive Prostate Cancer". ClinicalTrials.gov. US National Institutes of Health. 29 June 2017.
  21. ↑ 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". International Journal of Radiation Oncology, Biology, Physics. 65 (4): 965–74. doi:10.1016/j.ijrobp.2006.04.029. PMID   16798415.
  22. ↑ "Sipuleucel-T and ipilimumab clinical trials". ClinicalTrials.gov. US National Institutes of Health. 23 August 2017.

PD-icon.svg This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.