Over the years, castrate-resistant prostate cancer (CRPC) has created treatment dilemmas for physicians because the patient population represents a variety of stages and symptoms of the disease which takes the lives of approximately 30,000 men each year.
In recent years, a number of studies have led to more advanced treatment options that are adding months, and in some cases years, to the lives of these patients. A variety of new, FDA-approved therapies are targeted to specific symptoms and stages of the disease. This progress is giving hope to patients that further studies will lead to more breakthroughs soon.
Urologist George W. Adams, Jr., MD, and his colleagues at Urology Centers of Alabama are employing some of these new treatments and have participated in some of the studies. “I’ve been in practice for 35 years, and the last two to three years have been amazing in the number of drugs approved by the FDA for treating prostate cancer,” Adams says. “A large percentage of these patients die in two to three years without therapy, so it is exciting to have these options.”
When a patient is diagnosed with prostate cancer, initial treatment is based on the patient’s age, overall health, the volume and aggressiveness of the cancer, and the presence or absence of metastasis. After consultation with a surgeon and a radiation oncologist, the patient will have the information needed to make an educated decision on the course of treatment. Care options may include active surveillance if the cancer is not advanced. “In older men, this option may be sufficient, but younger men may need more aggressive therapy,” Adams says. “Some patients may choose the option of having a radical prostatectomy, the majority of which are performed robotically in the United States. Other treatment options include Intensity Modulated Radiation Therapy (IMRT) or radioactive seeds (brachytherapy).”
Adams says that the goal is to have a PSA score of zero following surgery. “If the PSA starts to rise after the patient has surgery, we will re-evaluate and may do radiation,” he says. “If the PSA starts to rise after surgery and/or radiation, the man is given hormone therapy at some point. The hormones chemically castrate him to decrease the cancer cell growth because the cells are feeding off of the testosterone in the man’s body.”
In the majority of patients, the PSA will eventually rise and consistent elevation generally indicates the presence of cancer cells. At that point, their cancer becomes classified as hormone-resistant, Adams says, and the cancer cells will continue to grow. The disease will eventually metastasize to bones or lymph nodes.
“Prior to the last few years, we didn’t have much to offer these patients except the chemotherapy drug Taxotere® (docetaxal) which is administered by an oncologist,” he says. “But the drug has dangerous side effects, including low white blood cell count, sepsis, and neuropathy.”
Once the cancer has metastasized, a new drug, Provenge (sipuleucel-T) can offer immune therapy to slow the growth of the disease. In clinical trials, the Provenge “vaccine” extended survival by a median 4.1 months, but some of the patients are still living years after the treatment. “The ideal candidate is a patient with little metastasis or few involved lymph nodes with a PSA of less than 20,” Adams says. “These people are not overwhelmed by the cancer yet and with this treatment may live six to 12 months longer.”
Physicians at Urology Centers of Alabama participated in the Provenge trial. “The patient first goes to the Red Cross to have his veins assessed to make sure he is a candidate for the leuka phoresis procedure which removes at least 100,000 white blood cells through IV’s in each arm,” Adams says. “We then send those cells to a facility in Atlanta where they are treated with antibodies for prostate cancer. Three days later, we infuse the treated cells into the patient’s body with a regular IV. After 10 days, we do another treatment. We perform this cycle three times.”
Adam adds that if a patient has good veins, he can finish the cycles in about 30 days. However, most of these patients are in their 70s and 80s and may have to have a port surgically placed in order to have the blood drawn. “For some men, the process is complicated, but it is tolerated well,” he says. “Some will have chills and fever, but those symptoms usually go away quickly.”
For the patients who have an increasing PSA, new bone lesions or more involved lymph nodes, an FDA-approved drug called Zytiga® (abiraterone acetate) can be used to prolong life by an average of four months. Because this medicine shuts down the adrenal glands completely, it must be given with prednisone. Side effects can be serious and include high blood pressure, low blood potassium and fluid retention. “Zytiga drops the PSA significantly,” Adams says, “and the patient can continue to take it as long as he responds to the treatment and has no major side effects.”
If the patient’s PSA continues to rise following this treatment, chemotherapy is the next option. If he continues to worsen following chemotherapy, he can take a new oral drug called Xtandi (enzalutamide), also approved by the FDA. Xtandi is an androgen inhibitor and is designed to interfere with the ability of testosterone to bind to prostate cancer cells.
“Xtandi is a promising drug, but a patient must have chemotherapy treatments before he can take it,” Adams says. “In the future, we think Xtandi will be approved for use before chemotherapy. If so, we may use it instead of Zytiga since you don’t have to use prednisone with it and it has fewer side effects.”
Some patients with extensive bone metastasis will develop severe bone pain and must rely on narcotic medicines for relief. When taken daily, such drugs can cause constipation and general malaise. A new FCA-approved medicine, Xofigo, can help with the pain and improve the patient’s daily life.
Xofigo, a radioactive isotope, is administered via IV by a radiation oncologist. The medicine goes directly to the bone to relieve the pain. “Xofigo can be given once a month for up to six doses,” Adams says. “While it was approved just for relief of bone pain, use of this medicine has proven to extend the lives of some patients for three to four months. Physicians can refer patients to Trinity Medical Center, Princeton Baptist Medical Center, and Brookwood Medical Center for the procedure.”
Adams appreciates the variety of therapies now available for patients. “We have a lot of things now that we’ve never had before which may allow urologists to keep patients in their practice longer before referring them to an oncologist. I can see the urologist and oncologist working in unison to treat these patients in the future,” Adams says.
The staff at Urology Center is participating in a national trial beginning in October that will evaluate a drug that is an androgen receptor blocker. Test participants will be men with CRPC who have a rising PSA but no metastasis. There will be a placebo phase of the trial, and the men will not be able to know their PSA scores during the trial.
“We are excited about the study, but there will be some men who are not willing to participate because of the one-third chance of receiving the placebo and not knowing their PSA scores,” Adams says. “I think the future looks good, although right now we aren’t curing anyone. We are using these drugs to extend their lives. Our hope is for progression-free survival so prostate cancer patients can enjoy their lives and their families.”
