Investigators at MUSC Hollings Cancer Center are conducting a clinical trial to determine whether changing the order in which certain treatments for metastatic prostate cancer are administered can prolong life for men with the disease. The study will also look at whether genomic markers can predict which patients will respond best to the approach.
Typically, patients with newly diagnosed metastatic prostate cancer are given hormone-blocking injections that trick the body into halting its production of testosterone, which can starve the cancer and help to prevent it from dividing and spreading. While this approach can improve symptoms and add time to a patient’s life, the cancer will eventually learn to grow without the presence of testosterone, says Hollings oncologist Todd Gourdin, M.D., the study’s principal investigator. This means the approach is often not a long-term fix.
“Inevitably, typically at about 18 to 24 months after starting treatment, the cancer develops a resistance,” said Gourdin. Doctors track prostate-specific antigen (PSA) in the blood to see how a patient is responding to treatment. “You’ll see that a patient’s testosterone is still low, the shots are doing what they’re supposed to be doing, but the patient’s PSA starts rising again. This means that even though testosterone is low, the cancer has learned to outsmart that therapy.”
When the cancer becomes resistant to the hormone-blocking injections, the next step in treatment is to administer a chemotherapy drug called docetaxel. But, since chemotherapy is most effective at targeting cells that are rapidly dividing and hormonal therapies keep the cancer cells from dividing, giving chemotherapy after the hormone-blocking injections may prevent it from being fully effective.
With this reasoning in mind, researchers from Hollings are testing to see if giving patients chemotherapy before beginning them on hormonal therapy is safe and can extend the time these patients have with their friends and families.
The Phase II trial, which was designed by Hollings researchers, has enrolled more than 50 men across three sites in the eastern United States. All patients are given four doses of docetaxel before being placed on the hormone-blocking injections intended to lower their testosterone, followed by two additional doses of chemotherapy. Primary outcomes are being measured based on how low the researchers can get each patient’s PSA level, which correlates with overall survival.
“This approach is not going to start curing these men, but if it can help them live longer just by making a pretty simple tweak, then I would be excited about that. Simply changing the order of the treatments is an easy fix, and it doesn’t cost any extra than the regular treatment.”
– Dr. Todd Gourdin
The study is the only one of which Gourdin is aware that has looked at administering chemotherapy while a patient’s testosterone level is still normal. However, prior studies have found that giving chemotherapy earlier in treatment, such as within a few months of beginning hormonal therapy, can improve outcomes. One large trial demonstrated a year and a half survival advantage for men who received docetaxel earlier in their treatment.
“A year and a half may not sound like a lot, but a lot of prostate cancer patients are in their 70s and 80s, so statistically, a year and a half makes a big difference,” said Gourdin.
Prostate cancer is the second most common cancer in American men, with one in nine men in the U.S. being diagnosed in their lifetimes. While there are effective ways to manage its symptoms and control its spread, there are currently no treatments that can cure advanced prostate cancer, which is the second leading cause of cancer deaths in American men.
“There are a lot of options for treating prostate cancer, but most men with metastatic prostate cancer still die, and we would like to change that,” said Gourdin. “Unfortunately, this approach is not going to start curing these men, but if it can help them live longer just by making a pretty simple tweak, then I would be excited about that. Simply changing the order of the treatments is an easy fix, and it doesn’t cost any extra than the regular treatment.”
The trial is still ongoing, but early results indicate that the strategy appears safe. Few men have experienced disease progression while on chemotherapy prior to beginning the hormonal therapy, and there have not been any adverse events from delaying the hormone-blocking injections.
Another component of the study involves using a liquid biopsy that allows researchers to detect tumor DNA in the blood and run genomic analyses. Gourdin hopes this arm of the trial will provide insight that could potentially predict which patients will do particularly well with this approach based on genomic markers.
“I think most oncologists see that genomics and personalized medicine are becoming increasingly important,” said Gourdin. “Up until recently, the way that we divided up treatment was based on race or by volume of disease. We would like to find better markers than that – specifically genomic markers that actually suggest which treatment is best for a particular patient.”
If the efficacy of this approach shows potential for being better than the current standard treatment, additional larger studies may be worthwhile to determine whether it improves long-term survival. For now, Gourdin hopes that the trial will show that a lower PSA was achieved in the men who enrolled and provide more insight into how to help more men in the future.