Matthew Rettig, MD:
Hi, my name is Matt Rettig. I'm a GU medical oncologist at UCLA and the affiliated VA Medical Center in Los Angeles. I'm also the Director of the Prostate Cancer Program at UCLA. I'm here with my patient, Dr. Jeff Ardell.
Jeffrey L. Ardell, PhD, FAHA:
My name is Jeff Ardell. I am Research Director of the Arrhythmia Program over at UCLA. My focus is in neurocardiology and understanding how to treat heart disease. So prostate cancer was way outside of my wheelhouse.
Matthew Rettig, MD:
So back in, I think it was 2018, you had an elevated PSA. What happened at that time? What are your recollections on what you felt, and how was it that you made it to my clinic?
Jeffrey L. Ardell, PhD, FAHA:
Well, actually we didn't even know it was prostate cancer initially. I was on a trip up to Hearst Castle with my wife, and I got a stabbing back pain, and it was quite intense. We came back, and they started doing a whole bunch of tests on me trying to figure out what it was, and they actually had me scheduled for a laminectomy to look at a mass they'd identified on the spinal cord area. They happened to do the PSA, and the PSA was elevated to 190. They decided not to do laminectomy, which was good, and basically referred me to your clinic, and that's where our relationship started.
Matthew Rettig, MD:
So that was back in 2018. At that time we had learned that the standard backbone of treatment with a hormone therapy that suppresses testosterone, something like Lupron or leuprolide, is a key element of the treatment. We also had learned very recently that adding another hormone agent, and in your case it was Zytiga or abiraterone, with low doses of prednisone really improves the ability to control the cancer and most importantly, makes patients live longer. So we put you on that therapy. How did it go for you? What were some of the key side effects or issues for you on the hormone therapy?
Jeffrey L. Ardell, PhD, FAHA:
Well, obviously dealing with various aspects of loss of testosterone, it's an impact on the entire family, but it is something that you can go through. I mean, my energy levels went down a little bit. Obviously intimacy was impacted by it, but this is something that you have to go through with this therapy.
I would like to point out at that time you also recommended to me that we try the PSMA scan, which was something at that time which was experimental. I actually paid for the first one myself. It was a little bit frightening because when we got the scan back, I lit up like a Christmas tree. It was all the way up from the thorax into the abdomen into the pelvic region. It's a little bit daunting to see that, but I knew I was in good hands, and we started the hormone therapy, and it was actually quite effective for a very long time.
Matthew Rettig, MD:
So overall you were also able to work during this time, full time, and continue your research efforts, isn't that right?
Jeffrey L. Ardell, PhD, FAHA:
Oh, yes. No, I am a tough old goat, and so I basically continue to work. I'm close to 71 years old. I continue to work quite significant hours here at UCLA. I have five NIH grants, so I'm keeping myself pretty busy.
Matthew Rettig, MD:
So ultimately after you had had a fairly good run with the hormone therapy, Lupron and the Zytiga, we did notice at one point that your PSA started to come up, and there was evidence of progression on scans. Since then you've had a number of other treatments. You were enrolled in an early Phase I study of a novel immunotherapy, something called a BiTE or bispecific T-cell engager, which was an industry-sponsored study in which a modified antibody, if you will, attaches to a protein on the surface of cancer cells, specifically PSMA, and immune cells called T-cells and attaches to something called CD3 on the T-cells. You were on that, you were one of the longest patients who responded to that therapy. Tell me your recollections, especially of the initiatives that required hospitalization and also how you handled it when it was administered as an outpatient.
Jeffrey L. Ardell, PhD, FAHA:
Well, that's a very, very good point. I'd also like to point out to people that, as you told me, prostate cancer is a multi-faceted disease and that every place it goes it changes a little bit differently. So I liken it to a forest fire. Sparks go everywhere, they change, they start new fires, and each treatment is successful for a while, but then it starts to lose efficacy.
One of the things I've been very impressed with Dr. Rettig and his team is they've always kept me informed of the options. There's always options, and you take a positive attitude going forward. So we did the energy deprivation therapy, and basically that helped us distinguish between what's called castrate-sensitive and castrate-resistant prostate cancer. What happened is, as Dr. Rettig said, my prostate, after a reasonable time, I think it was about 15 months, PSA started to go up, and Dr. Rettig suggested we try this immunotherapy.
So we went into the immunotherapy and for the first five cycles, I had to do it in hospital because this was a Phase I trial. This is a trial where you're really looking for safety and efficacy, not so much efficacy, but mostly safety. So I'd go into the hospital and they'd give me the drug and basically you're using your own immune system to fight the cancer cells, and it's a wonderful treatment. But it did come with some side effects. I mean, the reason they put you in the hospital is because it would mess with my thermoregulatory system, it would mess with my GI system. The first three or four times, it was a bit tough in terms of you would have some reactions. But the joy that came out of it is when we started doing the PSAs, within the very short period of time, they'd gone from 60 down to almost non-detectable. So we were both very excited.
After we got through this, we switched to the outpatient version of it, and the outpatient was done in the same building where I work. So I'd just take the elevator down and I figured out with Dr. Rettig the appropriate combination of anti-nausea medications and some pain medications. Really it became just a sort of a boring day sitting there getting the infusions, and everything went quite well. We did that for, I think around seven or eight months. Then unfortunately the prostate cancer cells that remained started to outfox the T-cells, and we then moved on to the next step.
What I'd like patients to realize is that ultimately this is a chronic disease. Things are going to work for a while, and then they're not going to work so well for a while. The trick is to keep in contact and communication with your primary care physician and your oncologist and then decide what's the next logical step.
Matthew Rettig, MD:
Yeah, I think that's a really good point is to take the mindset that metastatic prostate cancer is a chronic disease. I think one of my philosophies or approaches to treating advanced prostate cancer is to try to get any individual patient exposed to as many different treatments, whether they're standard of care treatments that any doctor could write a prescription for or clinical trials and to try to think of the sequence of these various potential treatments and how to optimize that sequence so that the total number of treatments is as great in number as possible. I think individual patients can benefit from that approach. Of course, not all patients are suitable for clinical trials or they may not have access to clinical trials or they may have other problems that make them difficult to receive some standard of care medications. Dr. Ardell has been really great. He's been a great patient, easy to work with, easy to talk to. Clinical trials have been a real important piece to the overall treatment strategy.
After the immunotherapy failed to control the cancer and the PSA was going up, we did some more scans including a PSMA scan, and we saw that the cancer remained where it had been, which is really restricted to the bones. We decided on a treatment called Radium 223. It goes by the brand name called Xofigo. It's a calcium mimetic. Radium has a very similar characteristic property as calcium, so it homes to the bone where there's sort of a reactive process in the bone, which is what prostate cancer does. It elicits a local bone-forming reaction. So the radium is an injectable form of radiation that will home to the areas in the bone where the prostate cancer is. It's in effect a systemic therapy, systemic radiation therapy that is. We did that for six doses given every month. Tell us about your experience with the radium.
Jeffrey L. Ardell, PhD, FAHA:
Actually, it was quite simple. You just went in, you got the injections. I really didn't notice any major impact from it. I'd also gone, which we haven't talked about yet, I'd also gone through a bunch of spot radiation treatments. Those were interesting as well because of the confinement you have to go in when you go into this space age machine for the spot radiation. But the surface radiation became ... I got my maximum exposures, that's why we switched to the injectable. It worked quite well and did very well and actually did a great job of knocking down the PSA areas in the bone. So I was quite pleased with that one.
Matthew Rettig, MD:
The radium is a treatment that has a finite course. We use up to six doses. So even when it's working, the patient may have their disease under control, at the end of six doses, you're still faced with a question as to what to do next. That was where we were I think in the most recent decision point as to what are the next treatments. I think given what was happening with your scan and the PSA, we decided that a chemotherapy drug would be a very reasonable approach, chemo being taxotere or docetaxel, probably the most commonly-used chemotherapy drug for prostate cancer.
But we also had a clinical trial at UCLA, a Phase III study, which was asking the question whether or not adding a second medication or medication to the docetaxel can improve the control of the cancer and actually make patients live longer. This was a drug called an AKT inhibitor, and half the patients get it, half the patients get a matched placebo, but all patients are getting the standard of care docetaxel. So you're on that treatment now. You enrolled in that clinical trial.
Jeffrey L. Ardell, PhD, FAHA:
First of all, let me say that I was terrified of chemotherapy. It was the one that I always kept pushing to the back of the thing because I'd heard some horror stories about it. So that went there. I finally said, "Well, okay, it's time to do the chemotherapy." Chemotherapy has gone wonderfully. I mean, the facility is nice. The personnel are nice. They go in, they take my blood to make sure I'm in reasonable shape. I lay in a lounge chair, they infuse it over an hour. Really the major thing you can see in me is I've lost most of my hair. But my granddaughter, who's nine years old, actually 10 years old now, got the honor of shaving my hair off, and that was a big moment for her. But other than that, it's been really quite nice. I have not had any nausea. I've had a little bit of neuropathy in my feet, but it's not too bad.
Obviously I'm immune-compromised to a certain degree, so I have to be careful when I'm out and about. But overall, it's gone great, and probably more importantly, the PSA levels have gone down now by about 60% just in the first four treatments. I've still got six more treatments to go. So I'm actually quite encouraged. One of the things that made me feel good about this too is Dr. Rettig described to me a patient of his who'd had similar chemotherapy who had essentially been able to be essentially on a treatment holiday for quite a long time because their PSA levels stayed down. After five years of this, I'd have to say I look forward to hopefully having the same response and having a treatment holiday.
The other thing I'd like to tell the people out there who are listening is don't be afraid of clinical trials. Just because you hear clinical trial, it does not mean that it's experimental. What they basically do is they're never going to take away the standard of care. They're going to take something else and add to it and see if they can improve the situation. What you're doing is you're not only potentially helping yourself, you're also helping patients down the line, and this is a long line of investigation that is going to hopefully get to a point where this disease is managed even better than it is today. So I've been honored to be part of two clinical trials, and will be glad to be part of additional ones if that's the appropriate step. Right now, we're pretty much set through March with the chemotherapy. At that point, we'll reassess with the scans and the PSMAs, and we'll see where we are. Then Dr. Rettig and I will sit down together along with my wife and make the decision where we are and where we go from there.
Matthew Rettig, MD:
Yeah, I think the point about not being fearful of a clinical trial is really key. We do know that historically patients with any cancer that enroll in clinical trials do better than those patients that don't. Clinical trials can really offer excellent opportunities for novel treatments. So you're not only going to help yourself, but you can also help the world with growing our understanding of the management of various cancers including prostate cancer.
Ultimately, after the chemotherapy we'll have a number of different options. I think one option that is particularly appealing is the PSMA-based radiation for patients whose cancer have this protein called PSMA on its surface, and that's about 90% of prostate cancers. We have another systemic injectable form of radiation where an inert chemical can attach to PSMA, and that inert chemical is linked to a radioactive element that emits cancer-cell killing radiation, what's called ionizing radiation. This is relatively new, approved within the last couple of years for patients who've had chemotherapy. In the near future, I suspect pretty imminently, we will have the same approval for patients who have not had chemotherapy. So I think that's another important option that we can discuss in addition to other clinical trials as well as other standard of care options. I think all in all things have gone well with the current clinical trial, as you've pointed out. That's kind of where we are at this point, at this juncture in the journey.
Jeffrey L. Ardell, PhD, FAHA:
Yeah. I'd like to also point out that the attitude you take into this as a patient is important. Being positive, having a focus on life, a focus on living your life, a focus on trust in your care team, that's important. I mean, like you said, there's actually quite a bit of research that indicates that the spiritual aspect of your treatment and the spirit you go into it has a huge impact on how you turn out. You don't take a defeatist attitude into it. You don't go to say, "Why me?" You just sit there and say, "Okay, what's next? Let's fight this dang thing." My other suggestion is, like I said, is get to the best doctor you can, listen to what they say, talk with them, discuss the options. They'll be very straight with you, and then just move forward and just live your life.
Matthew Rettig, MD:
I would also say that if any patient feels the need to do so, please, you can get a second ... Any doctor should be open to getting a second opinion, especially if they may not have the expertise or access to clinical trials for prostate cancer. So that's I think another important piece. Get to someone who really has the expertise and access to studies that can potentially benefit you.
Jeffrey L. Ardell, PhD, FAHA:
For the spouses out there, my wife has been very engaged in some of the online platforms with spouse support, and that's been very helpful to her as well in terms of understanding what's going on with all of this stuff. Basically, I keep emphasizing, this is a chronic disease. This is not a death sentence. This is a chronic disease, and you just keep fighting.