Dr. Michael J. Morris is a medical oncologist who specializes in prostate cancer at Memorial Sloan Kettering Cancer Center in New York City where he serves as the Prostate Cancer Section Head.
He spoke with Prostatepedia about a clinical he’s running that looks at combining Taxotere (docetazel) and Xofigo (radium-223).
What attracted you to medicine in the first place? Why did you become a doctor?
Dr. Michael Morris: I came to medicine from a somewhat different background than many physicians. I grew up in a family that’s heavily focused on the humanities—history, culture, and literature. I inherited those genes from my family, but I also had a real scientific interest that I found to be equally compelling.
In college, I divided my time between literature and science. What attracted me to medicine was that it perfectly merged humanism and science – both patient care and research require an understanding of the history of a patient, his disease, and his treatments. The challenge of medicine is to creatively conceive how biology can be brought to bear to alter these for an individual and the field.
Have you ever had any patients over the years whose stories have changed how you view either the art of medicine or your own role?
Dr. Morris: Many people feel absolutely devastated when they get prostate cancer, which for many people can be a chronic disease. The anxiety provoked by a cancer diagnosis, and even by a detectable or rising PSA can be existential. One of my patients was a Vietnam War veteran. He had been through his share of battles before, and saw more than a few of his closest friends not live past early adulthood. For him, prostate cancer was a reminder to him of what he had survived already. He felt that he was lucky to have lived long enough to face prostate cancer as the primary threat to his life. He took his prostate cancer journey as the next opportunity to lead, to teach, and to be in charge of and help so many people through their disease. Even in our waiting room, he was guiding people and keeping everybody’s anxiety in line. That made a huge impression. People who have faced risks before can be incredibly helpful to those who are not experienced with the helplessness and fear that a cancer diagnosis provokes. We have a lot of first responders in our practice, and their experience managing risk and anxiety can be very helpful to those without those skills. They can help the care providers as much as the patients, too.
From a clinical trial standpoint, I’m struck by the selflessness of so many of our patients. They understand that their treatments are the result of the efforts of patients on studies who have preceded them, and they’re willing to volunteer so that we can learn how to best treat those patients who will follow them. They’re saying, “I’m going to give my body to a clinical trial so that the next generation of prostate cancer patients can learn from my experience.” That’s inspiring.
Talk to us about your Phase III trial combining Xofigo (radium-223) and Taxotere (docetaxel). Why this particular trial? Why now?
Dr. Morris: In general, my research focus is where nuclear medicine and medical oncology intersect. That is, looking at drugs that you can deliver systemically, that are targeted to either the prostate cancer cell itself or to the host organ of most metastatic disease which is bone. And that also means looking at combining those drugs with other drugs that can help patients either feel better or survive longer.
This trial comes out of a long history of work, trying to combine radioligand therapy, which are essentially liquid systemic radioactive drugs, with other systemic treatments, to target both the cancer cell itself and bone, which is the host organ to most metastatic disease.
Xofigo (radium-223) is a known, life-prolonging radioactive agent that targets metastatic disease to bone. Since most metastatic disease in prostate cancer is in the bones, you can really encompass most of the disease by targeting that one bony compartment. Within the bone is the cancer itself, and the chemotherapy is used to target the prostate cancer cell. It’s a concept of dual targeting, both the environment that the cancer is hosted in and the cancer itself. That’s why we’re using these two agents, one of which targets bone and the other cancer, and both of which prolong survival independently, to see if those effects can be amplified by giving them together.
What will you be doing step by step?
Dr. Morris: The first thing is, a man has got to qualify for the trial, which means that he has to have predominantly bone metastases because that is the target for the Xofigo (radium-223).
The second thing is that he can’t have a significant amount of soft tissue disease in either the lungs or the liver. He has to have progressed through standard testosterone-lowering agents, such as Zytiga (abiraterone) or Xtandi (enzalutamide). If that patient is otherwise a chemotherapy candidate, then the treatment involves giving chemotherapy once every three weeks and then the Xofigo (radium- 223) once every other chemotherapy dose, so every six weeks. They’re both IV agents. That’s the essence of the treatment of the study.
Xofigo (radium-223) is a unique radioactive drug. It emits an alpha particle, which releases a lot of energy in a very tiny distance, only a few cell-lengths deep. It has virtually no side effects, so it’s a well-tolerated, life-prolonging treatment.
Chemotherapy is standard first-line chemotherapy in the form of Taxotere (docetaxel). It’s given every three weeks. It’s life-prolonging as well, and is a member of a class of taxane-based chemotherapy.
What are the side effects like for that?
Dr. Morris: Primarily fatigue, but some patients can have tingling in their fingers and toes as well, and sometimes changes in taste. A very small number of patients can have their white blood cell counts suppressed.
How long are you going to be following these men while they’re on these two agents?
Dr. Morris: Patients receive a total of six doses of Xofigo (radium-223) and no more than ten doses of chemotherapy. After that, they’ve completed the treatment portion of the protocol, and they could go on, if they needed, to any other treatments. But we follow them for the rest of their lives.
Are there any fees associated with the trial? I’m assuming the Xofigo (radium-223) and the Taxotere (docetaxel) are provided.
Dr. Morris: The Xofigo (radium-223) is provided by the study, and the patient is responsible for the docetaxel, which is standard chemotherapy.
What else do you hope to learn from this study?
Dr. Morris: There are a whole host of innovative biomarkers and science that is built into this trial, so we learn as much as we can about each patient as they’re treated.
We’re looking at circulating tumor cells and cell-free DNA. We’re looking at the impact of the treatment using novel imaging techniques. We’re looking at quality of life. There’s a whole component of the study that will allow us to learn as much about the prostate cancer and the efficacy of the drugs as well.
Those will be covered under the trial as well, right?
Dr. Morris: Absolutely. Those are all covered by the study.
Is that information shared with the patient?
Dr. Morris: Any information we gather in real-time can be shared with the patient. Some of the scientific aspects of the trial will only be performed after the trial is done, so results from those will be delayed until after the study. But as we learn new information, we pass it on to our patients.