Sipuleucel-T, sold under the brand name Provenge, developed by

Dendreon Dendreon is a biotechnology company. Its lead product, Provenge (known generically as sipuleucel-T), is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells (autologous, with dendritic cells thought to be ...

Pharmaceuticals, LLC, is a cell-based

cancer immunotherapy Cancer immunotherapy (sometimes called immuno-oncology) 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 ...

for prostate cancer (CaP). It is an autologous cellular immunotherapy.

Medical uses

Sipuleucel-T is indicated for the treatment of

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

, asymptomatic or minimally symptomatic, metastatic castrate-resistant

hormone-refractory prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surr ...

(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.

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 Leukapheresis () is a laboratory procedure in which white blood cells are separated from a sample of blood. It is a specific type of apheresis, the more general term for separating out one particular constituent of blood and returning the remain ...

procedure. * The blood product is sent to a production facility and incubated with a fusion protein (PA2024) consisting of two parts: ** The

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

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.

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.

Society and culture

Legal status

Sipuleucel-T was approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) on April 29, 2010, to treat asymptomatic or minimally symptomatic metastatic HRPC. 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.

Research

Clinical trials

Completed

Sipuleucel-T showed

overall survival Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...

(OS) benefit to patients in three double-blind randomized

phase III clinical trials The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

, 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. 31.7% of treated patients survived for 36 months vs. 23.0% in the control arm. 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. 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). 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.

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. Its purpose is to test efficacy for patients whose CaP is still controlled by either suppression of

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

by hormone treatment or by

surgical castration Inguinal orchiectomy (also named orchidectomy) is a specific method of orchiectomy whereby one or both testicles and the full spermatic cord are surgically removed through an incision in the lower lateral abdomen (the "inguinal region"). The p ...

. Such patients have usually failed primary treatment of either surgical removal of the prostate, (

EBRT External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachyt ...

), internal radiation,

BNCT Neutron capture therapy (NCT) is a type of radiotherapy for treating locally invasive malignant tumors such as primary brain tumors, recurrent cancers of the head and neck region, and cutaneous and extracutaneous melanomas. It is a two-step pro ...

or (

HIFU High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that uses non-ionizing ultrasonic waves to heat or ablate tissue. HIFU can be used to increase the flow of blood or lymph or to destroy tissue, such as tumors, via ...

) 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 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. Cytotoxic T lymphocytes (CTLs) can recogniz ...

(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.

References

External links

* {{Portal bar , Medicine Cancer treatments Prostate cancer