Sipuleucel-T

Sipuleucel-T
Vaccine description
Target disease prostate cancer
Type Protein subunit
Clinical data
Trade names Provenge
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a611025
Pregnancy cat.  ?
Legal status ℞-only (US)
Routes intravenous
Identifiers
CAS number 917381-47-6 Y
ATC code L03AX17
PubChem SID85151648
UNII 8Q622VDR18 N
KEGG D06644 Y
ChEMBL CHEMBL1237024 N
 N(what is this?)  (verify)

Sipuleucel-T (APC8015, trade name Provenge),[1][2] manufactured by Dendreon Corporation, is a therapeutic cancer vaccine for prostate cancer (CaP). It must be prepared specifically for each patient. In metastatic prostate cancer, it has extended survival by about four months. It costs $93,000 for a course of treatment.

Contents

Cancer Immunotherapeutic history

Sipuleucel-T is the first therapeutic cellular immunotherapy to demonstrate effectiveness in Phase III clinical trials by prolonging the life of patients who have advanced to the late stage of the disease, 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.[3][4][5]

First FDA-approved cancer vaccine

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.[6][7]

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 a source sanctioned by Medicare and used by major health care insurance providers to decide whether and when a treatment should be covered when a physician recommends it for established indications.[8][9]

While referred to as a therapeutic vaccine that treats the cancer, as compared to a preventive vaccine, which prevents infectious disease, Sipuleucel-T is an immunostimulant. As of 2011, there are two approved preventive vaccines which prevent the cancer-causing viruses human papillomavirus and hepatitis B virus.

Treatment method

A course of Sipuleucel-T treatment consists of three basic steps:

  1. A patient's own white blood cells, primarily antigen-presenting cells (APCs), also called Dendritic cells, are extracted in a leukapheresis procedure.
  2. The blood product is sent to the factory and incubated with a fusion protein (PA2024) consisting of two parts,
    1. the antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cells, and
    2. an immune signaling factor granulocyte-macrophage colony stimulating factor (GM-CSF) that helps the APCs to mature.
  3. The activated blood product (APC8015) is returned from the factory to the infusion center and re-infused into the patient to cause an immune response against cancer cells carrying the PAP antigen.[3][4]

A complete Sipuleucel-T treatment repeats three courses over the span of a month, with two weeks between successive courses.[10]

Survival benefit

Sipuleucel-T showed overall survival (OS) benefit to patients in three double-blind randomized phase III clinical trials, D9901,[4] D9902a,[11][12] and IMPACT.[3]

The D9901 trial[4] 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[11] 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.

The IMPACT trial[3] served as the basis for licensing approval of Sipuleucel-T by the FDA. 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. Overall survival was statistically significant (P=0.032).

Side effects

The side effects of Sipuleucel-T were mostly limited to chills, fever, fatigue, nausea and headache which usually occurred within the first few days of treatment. In addition, more serious cardiovascular events were observed at a rate of 2.4% in patients treated with Sipuleucel-T vs 1.8% in placebo-treated patients.[3]

Additional clinical trials

The PRO Treatment and Early Cancer Treatment (PROTECT) trial, a phase IIIB clinical trial started in 2003, is ongoing.[13] 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).[14]

Cost of treatment

The total cost for three courses of treatment with Sipuleucel-T is $93,297.60.

References

  1. ^ 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. 
  2. ^ US granted 6210662, Laus R, Ruegg CL, Wu H, "Immunostimulatory composition", published 2001-04-03, assigned to Dendreon Corporation (Seattle, WA) 
  3. ^ a b c d e 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". N. Engl. J. Med. 363 (5): 411–22. doi:10.1056/NEJMoa1001294. PMID 20818862. 
  4. ^ a b c d 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". J. Clin. Oncol. 24 (19): 3089–94. doi:10.1200/JCO.2005.04.5252. PMID 16809734. 
  5. ^ Longo DL (July 2010). "New therapies for castration-resistant prostate cancer". N. Engl. J. Med. 363 (5): 479–81. doi:10.1056/NEJMe1006300. PMID 20818868. 
  6. ^ Richwine L (2010-04-29). "U.S. FDA OKs Dendreon's prostate cancer vaccine". Reuters. http://www.reuters.com/article/idUSN2919838820100429. Retrieved 2010-04-30. 
  7. ^ "Approval Letter - Provenge". Food and Drug Administration. 2010-04-29. http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210215.htm. 
  8. ^ "NCCN Guidelines and NCCN Compendium Updated". http://www.nccn.org/about/news/international_ebulletin/2010-07-26/guidelines_compendium.asp. Retrieved 2011-01-08. 
  9. ^ "NCCN Drugs & Biologics Compendium". http://www.nccn.org/professionals/drug_compendium/content/contents.asp. 
  10. ^ "Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon". Drugs R D 7 (3): 197–201. 2006. PMID 16752945. 
  11. ^ a b 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. 
  12. ^ Mason K (2005-11-02). "New treatment options for patients with prostate cancer". ECCO-the European CanCer Organisation. http://www.eurekalert.org/pub_releases/2005-11/foec-nto110205.php. 
  13. ^ "NCT00779402: Provenge for the Treatment of Hormone Sensitive Prostate Cancer". ClinicalTrials.gov. US National Institutes of Health. http://clinicaltrials.gov/ct2/show/NCT00779402. 
  14. ^ 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. doi:10.1016/j.ijrobp.2006.04.029. PMID 16798415. 

External links

 This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms".

Endogenous
Other protein/peptide
Other
Exogenous

M: LMC

cell/phys/auag/auab/comp, igrc

imdf/ipig/hyps/tumr

proc, drug(L3/4)