Sipuleucel-T
Encyclopedia
Sipuleucel-T 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.
s 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.
(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 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.
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
.
A complete Sipuleucel-T treatment repeats three courses over the span of a month, with two weeks between successive courses.
(OS) benefit to patients in three double-blind randomized phase III clinical trials, D9901, D9902a, and IMPACT.
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.
The IMPACT trial 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).
of 2.4% in patients treated with Sipuleucel-T vs 1.8% in placebo-treated patients.
Dendreon
Dendreon is a Seattle based biotechnology company. Its lead product, Provenge , is an immunotherapy for prostate cancer...
Corporation, is a therapeutic cancer vaccine
Cancer vaccine
The term cancer vaccine refers to a vaccine that either prevents infections with cancer-causing viruses, treats existing cancer or prevents the development of cancer in certain high risk individuals...
for prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
(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.
Cancer Immunotherapeutic history
Sipuleucel-T is the first therapeutic cellular immunotherapy to demonstrate effectiveness in Phase III clinical trialClinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s 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
Prostate cancer staging
Prostate cancer staging is the process by which physicians categorize the risk of cancer having spread beyond the prostate, or equivalently, the probability of being cured with local therapies such as surgery or radiation. Once patients are placed in prognostic categories, this information can...
designation is T4,N1,M1c.
First FDA-approved cancer vaccine
Sipuleucel-T was approved by the U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(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
National Comprehensive Cancer Network
National Comprehensive Cancer Network is an alliance of twenty-one cancer centers in the United States, most of which are designated by the National Cancer Institute as comprehensive cancer centers...
(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.
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
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
and hepatitis B virus
Hepatitis B virus
Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China...
.
Treatment method
A course of Sipuleucel-T treatment consists of three basic steps:- A patient's own white blood cells, primarily antigen-presenting cells (APCs), also called Dendritic cells, are extracted in a leukapheresisLeukapheresisLeukapheresis 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 remainder to the circulation.Leukapheresis may be performed to...
procedure. - The blood product is sent to the factory and incubated with a fusion protein (PA2024) consisting of two parts,
- the antigen prostatic acid phosphataseProstatic acid phosphataseProstatic acid phosphatase , also prostatic specific acid phosphatase , is an enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer or other diseases....
(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 antigen prostatic acid phosphatase
- 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.
A complete Sipuleucel-T treatment repeats three courses over the span of a month, with two weeks between successive courses.
Survival benefit
Sipuleucel-T showed overall survivalSurvival rate
In biostatistics, survival rate is a part of survival analysis, indicating the percentage of people in a study or treatment group who are alive for a given period of time after diagnosis...
(OS) benefit to patients in three double-blind randomized phase III clinical trials, D9901, D9902a, and IMPACT.
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
P-value
In statistical significance testing, the p-value is the probability of obtaining a test statistic at least as extreme as the one that was actually observed, assuming that the null hypothesis is true. One often "rejects the null hypothesis" when the p-value is less than the significance level α ,...
).
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.
The IMPACT trial 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 rateof 2.4% in patients treated with Sipuleucel-T vs 1.8% in placebo-treated patients.