Prostate cancer treatment has had a lot more options come available in the past few years. The latest prostate cancer treatments include thermal-enhanced metastatic therapy, vaccines, medications, and potential new drug therapies as well as as gene, virus, and cells that are like stem cells.
TEMPT (Thermal-Enhanced Metastatic Therapy)
Thermal-Enhanced Metastatic Therapy (TEMT) is a potential new treatment involving iron nanoparticles that are deposited on the surface of prostate cancer cells. According to Robert H. Getzenberg, PhD, director of Research at Brady Urological Institute, researchers are capitalizing on the fact that heat changes the organization of the nucleus of cancer cells to develop a new treatment for the disease. Once the nanoparticles are on the surface of the prostate cancer cells, clinicians can use a special magnetic device that is similar to an MRI (magnetic resonance imaging) scan to quickly heat the nanoparticles, but not the body temperature. Raising the temperature of prostate cancer cells makes them susceptible to chemotherapy and radiation.
Some of the latest prostate cancer treatments are vaccines.
Provenge (sipuleucel-T) was approved by the FDA on April 29, 2010, for men who have asymptomatic or minimally symptomatic metastatic hormone resistant prostate cancer. Sipuleucel-T is referred to as a vaccine because it has immunotherapy activity – it makes cancer cells susceptible to attack by the immune system. Specifically, Provenge works by stimulating the immune system to recognize a protein called prostatic acid phosphatase (PAP), which is found in about 95 percent of all prostate cancer cells. In clinical trials, men with advanced prostate cancer who took Provenge lived an average of 4.5 months longer than men who did not receive the vaccine. Side effects include back pain, chills, fatigue, fever, headache, joint pain, and nausea. Serious reactions may include stroke and acute infusion reactions. Doses of sipuleucel-T are prepared individually for each patient, using his own immune system cells, which makes the drug extremely expensive at about $100,000 per treatment course. Read more about the latest prostate cancer treatments here.
Another vaccine, PROSTVAC-VF, is entering Phase III clinical trials in late 2010. Thus far, trials show that 30 percent of men who received the vaccine were alive after three years compared with 17 percent who took placebo. The vaccine was tested in men with metastatic prostate cancer who did not respond to hormone therapy. Go to PROSTVAC-VF Website.
Pharmaceutical treatments have provided some of the most recent prostate cancer treatments.
In June 2010, the Food and Drug Administration approved Jevtana (cabazitaxel). This is the first drug shown to extend the life of men who no longer respond to hormone treatments or to another chemotherapy drug called docetaxel. Cabazitaxel is given via injection and used along with prednisone. The drug works by preventing the formation of structures that pull apart the chromosomes in prostate cancer cells. In a study that compared use of Jevtana with standard treatment in men who had prostate cancer that was not responding to therapy, those who received Jevtana injections lived an average of 10 weeks longer than men in the standard treatment group. Jevtana did not cause complete remission or elimination of signs of the disease in any of the men. Side effects included a decline in levels of white blood cells (which fight infections), anemia, lower levels of blood platelets (which increases risk of bleeding), diarrhea, fatigue, nausea, vomiting, constipation, weakness, abdominal pain, back pain, fever, hair loss, anorexia, and kidney failure. Go to Jevtana Website.
Xofigo (radium-223) is a radiopharmaceutical for treatment of late stage hormone-resistant prostate cancer that has metastasized to the bone but no other organs. Xofigo was approved by the FDA on May 15, 2013. It is an injectable drug given every four weeks for six weeks that uses radiation from radium-223 decay to attack and kill cancer cells. Because radium is chemically similar to a common component of bone—calcium—the drug is attracted to cancer cells in bone. Xofigo uses short-wave alpha radiation instead of longer wave beta or gamma radiation, so the drug causes less damage to healthy tissue during treatment. Patients who took Xofigo lived a mean of 14 months compared with 11.2 months in men who took placebo. The common side effects include nausea, vomiting, diarrhea, and swelling of the leg, foot, or ankle. It is marketed by Bayer.
Several prostate cancer treatments fall under hormone therapy.
On April 28, 2011, the Food and Drug Administration (FDA) approved abiraterone (Zytiga), an oral medication for the treatment of metastatic advanced prostate cancer., In a Phase 3 clinical trial, abiraterone improved overall survival by an average of nearly four months when compared with placebo. The Phase III trial included 1,195 men who had advanced prostate cancer that had not responded to surgery or chemotherapy. One group of 797 men received abiraterone and prednisone while the control group received prednisone and a placebo. Men in the abiraterone treatment group lived an average of 14.8 months compared with men in the placebo group who lived an average of 10.9 months.
Abiraterone is a type of hormone therapy that works by inhibiting the activity of an enzyme that is involved in development of testosterone. Men in the abiraterone group were more likely to retain fluids and to experience a rise in blood pressure, urinary frequency, cough, muscle aches, hot flashes, diarrhea, heartbeat disorders, upset stomach, joint swelling, and upper respiratory tract infections.
Cabozantinib is an experimental drug that has been tested in a number of clinical trials against hormone-resistant prostate cancer, lung cancer, ovarian cancer, and thyroid cancer, and observed for its effectiveness against metastatic bone lesions in different tumors, including prostate cancer. Thus far, cabozantinib has been shown to work by interfering with the activity of two proteins, MET and VEGFR2, that are involved in the development and progression of cancer. In a Phase 2 trial, cabozantinib was given to 171 men who had hormone therapy resistant metastatic prostate cancer. More than three-quarters of the men had bone metastases. After 12 weeks of treatment, 76% of the men whose cancer had spread to the bone had partial or complete disappearance of the bone metastases. More than two-thirds of the study participants had some reduction in the spread of cancer outside of the bone. Use of cabozantinib was associated with fatigue, gastrointestinal symptoms, and high blood pressure.
Xtandi was approved for prostate cancer by the Food and Drug Administration (FDA) on August 31, 2012. Candidates for Xtandi (enzalutamide) must have advanced prostate cancer that has spread or recurred even though it was treated with hormone therapy and docetaxel (chemotherapy). Studies indicate that Xtandi works in two ways: by interfering with the testosterone and dihydrotestosterone receptors on prostate cancer cells, and by stopping the hormone receptors from exchanging messages with prostate cancer cells, which then stops cancer growth. According to the research, men who received Xtandi lived for an average of 18.4 months compared with men who took placebo, who lived for 13.6 months, or a 4.8 month overall survival benefit. Side effects may include anxiety, back pain, blood in the urine, diarrhea, dizziness, headache, high blood pressure, hot flush, lower or upper respiratory infections, muscle weakness, sleep problems, spinal cord compression, and tingling in the arms and legs.
Orteronel (TAK-700) is an oral, nonsteroidal drug that is being developed for treatment of men with metastatic hormone-resistant prostate cancer. The drug works by selectively inhibiting the activity of the 17,20 lyase enzyme in the testicles and adrenal glands. This enzyme is involved in the production of precursor molecules for male and female sex steroid hormones that contribute to the progression of hormone-resistant prostate cancer. After orteronel showed positive results in Phase 1 and 2 trials, two Phase 3 trials were initiated in early 2012. These studies will examine the impact of orteronel plus prednisone, or prednisone with placebo, in men who have metastatic hormone-resistant prostate cancer.
Gene therapy, also referred to as immune engineering, is an evolving treatment option for prostate cancer that has been the focus of more than 20 clinical trials. Gene therapy is the process of introducing genetically engineered material, usually DNA, into the body to fight an acquired or inherited disease. In cases of prostate cancer, the genes are placed into the prostate tumor, where they are designed to create an immune response against the cancer cells. Unlike drug therapy, which works for only a short time once it is inside the body, gene therapy continues to recognize the tumor and attempts to eradicate the cancer as long as there are cancer cells to eliminate, or to stimulate the patient’s immune system to fight the cancer. The long-term goal of gene therapy is to develop treatments that attack only cancer cells, which would in turn eliminate adverse effects on the body and improve the chance of eliminating the disease as well. (Alliance for Cancer Gene Therapy)
The most common way to deliver gene therapy to a tumor is via an adenovirus. Viruses can be used as delivery vectors once scientists alter them so they transport normal human DNA to the target prostate cancer cells rather than disease-causing genes. Once the target cells are infected with the vector, the vector releases its genetic material into the cancer cells with the goal of stopping the cancer.
Scientists are still exploring which genes, viral vectors, and strategies are optimal to ensure delivery of genetically modified material to tumor cells and to make sure they are accepted by the tumor. In the July 2010 issue of Human Gene Therapy, experts reviewed the progress being made in gene therapy for prostate cancer. Overall, most of the more than 90 clinical protocols using gene therapy in prostate cancer patients in the National Institutes of Health database used adenoviral vectors. While adenoviral gene therapy strategies in prostate cancer patients have proved to be safe thus far, scientists are still struggling to identify which approaches should be considered and improved. However, experts must first conduct randomized, well-controlled Phase 3 trials, and that point has not yet been reached. (Kochanek 2010)
Virus therapy, also known as oncolytic virus therapy, is a new potential treatment strategy for prostate cancer that is still in the early stages of study. A virus chosen to treat cancer is called an oncolytic virus, and once it is introduced to the prostate cancer cells, it replicates and kills tumor cells selectively. The progeny viruses produced within the cancer cells are then released, and they spread and infect other cancer cells that surround it. This cycle continues and results in the killing of more and more cancer cells. Because oncolytic viruses are not able to replicate in healthy cells, normal tissue is not damaged. Experts believe the development of oncolytic virus therapy will eventually lead to a promising treatment option for men who have prostate cancer. (Fukuhara 2010)
In a recent study published in the The Prostate, scientists reported that certain measles virus vaccine strain derivatives might prove to be effective in men who had advanced prostate cancer. They came to this conclusion after using a measles virus vaccine strain derivative called MV-CEA in prostate cancer cell lines and in mice. The scientists, who were from Mayo Clinic, found that the average survival time in the MV-CEA-treated mice was nearly double that of mice not administered the virus therapy, and complete regression of the tumor was seen in 20 percent of the treated animals. In the prostate cancer cell lines, virus therapy completely eradicated two of the three and nearly eliminated the third after seven days of treatment. (Msaouel 2009)
Treatment of Stem Cell-Like Cells
A yet-unknown type of treatment designed to attack stem cell-like cells is being explored by researchers at Lund University and Skane University Hospital in Malmo, Sweden. According to one of the investigators, Anders Bjartell, a professor at the Faculty of Medicine’s division for Urological Cancer Research, Skane University Hospital, “if you are not successful in eradicating that tumour cell population, there is a risk of subsequent uncontrolled growth of the tumour.”
Because cancer stem cells often do not respond to chemotherapy or hormonal therapy, researchers have been searching for a different way to eliminate these cells. So far, research efforts have turned up a protein called STAT3, which is active in stem cell-like cells, and a natural compound called galiellalctone, which has demonstrated an inhibitory effect on the growth of prostate cancer. Scientists are now working to develop substances that will inhibit STAT3, using galiellalctone as a model, with hopes of finding a way to attack stem cell-like cancer cells in men who have prostate cancer.
Fukuhara H., et al. Oncolytic virus therapy for prostate cancer. Int J Urol 2010 Jan; 17(1): 20-30
Kochanek S, Gansbacher B. Prostate cancer gene therapy: attempts to innovate. Hum Gene Therapy 2010 Jul; 21(7): 791
Msaouel et al. Engineered measles virus as a novel oncolytic therapy against prostate cancer. The Prostate 2009; 69(1): 82 DOI:10.1002/pros.20857