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SANTA MONICA
, Calif.
-- It can start as skin, lung or bone cancer, but when it's not stopped early, many cancers spread to the liver. Traditionally, once the disease hits the liver, patients are given less than a year to live. Now a new experimental approach is blasting the organ with chemo while sparing the rest of the body. The approach turned one man's grim prognosis upside down.
It's a story made for the movies. Retired navy fighter pilot Chris "Boomer" Wilson was one of the inspirations behind "Top Gun." Now he's an inspiration for cancer patients everywhere.
Wilson was diagnosed with melanoma, which spread to his liver.
"I knew enough about melanoma to know that if it metastasized, I was in big trouble." Wilson told said. "I was originally given a prognosis of 3 to 9 months.
He sought out Dr. Mark Faries, who was experimenting with a new treatment called percutaneous hepatic perfusion.
"PHP is a treatment that allows us to give very high doses of chemotherapy but keep them largely confined to the liver" Dr. Faries, associate member at the John Wayne Cancer Institute in Santa Monica, Calif., said.
Dr. Faries uses catheters to deliver 10 times the normal amount of chemo directly to the liver. Two balloons block the chemo from flowing through the rest of the body. The blood that does touch the chemo is filtered out, cleansed and pumped back in.
"So we can use enough chemotherapy to actually kill the tumor," Dr. Faries explained. "The other advantage is it spares the rest of the body much of the exposure."
In one study, nearly 80 percent of patients saw their tumors shrink or stabilize. After three treatments, Wilson's tumors shrank by more than 60 percent, and doctors say what's left is fading.
"It's like someone tells you you're gonna die in a month, and then the next day the same guy comes to you and says no you're not -- false start," Wilson said.
PHP is in the final phase of testing. Traditional treatment for metastatic liver cancer includes surgery and IV chemotherapy, but Dr. Faries says the success rate for those treatments is about 10 percent.
Blasting Away Liver Tumors -- In-Depth Doctor's Interview
Mark Faries
, M.D., director of translational tumor immunology at the John Wayne Cancer Institute in Santa Monica, Calif., talks about using PHP to give metastatic melanoma patients high doses of chemotherapy that are confined to the liver.
What is PHP, and what is the purpose of this Phase lll clinical trial?
Dr. Mark Faries: PHP is a treatment that allows us to give very high doses of chemotherapy, but keep them largely confined to the liver, and that allows us to treat tumors that we have been unable to treat before. The current trial is a Phase lll trial that is treating patients with metastatic melanoma. Melanoma can frequently go to the liver, and sometimes it goes only to the liver in many patients, particularly patients with melanomas that start in the eye. PHP is a way of delivering chemotherapy to the liver, but then what it allows us to do is to take the blood that goes into the liver with the chemotherapy and cleanse that blood to remove the chemotherapy from it, before it gets back into the patient’s general circulation so we can use several times what the normal maximum dose of chemotherapy would be. The importance of that is that for tumors like melanoma, which are generally very resistant to chemotherapy, it allows us to give enough chemotherapy that the tumors then begin to respond
Why is cleansing the blood beneficial for the patient?
Dr. Faries: What it allows us to do is to remove the vast majority of the chemotherapy before it gets into the general circulation. The main side effects of toxicities of the chemotherapy have to do with things like getting into the bone marrow or the GI tract and causing bone marrow suppression or bone ulceration of the intestine or stomach, so if we can avoid the chemotherapy getting to those areas, we avoid those complications or toxicities
If a patient came to you with melanoma that had spread to the liver, how would you treat them, in general?
Dr. Faries: Every patient is different. Some patients are able to have their cancer in the liver removed. Some tumors are types of tumors that do respond to more traditional chemotherapies, but for a patient with melanoma that is metastatic to the liver, our preference is to remove that, if possible. Unfortunately, the vast majority of the time, it’s not possible to surgically remove it. In the old days, they would get some form of chemotherapy or be on another form of treatment, which sometimes would work, but particularly with liver metastases, the incidence of responding to treatment was very low, generally in the 10 to 20 percent range, and many of those responses were quite short-lived. What this new treatment allows us to do is to get a much more reliable, immediate control of the tumor growth, and for a large number of patients, we’ve been seeing a very substantial shrinkage or disappearance of tumors that they have
Is metastatic melanoma tricky when it comes to the liver, or is it that the liver is a tricky place to deal with any types of cancer?
Dr. Faries: The liver is a critical organ. We obviously depend on it every minute of the day, so when cancer spreads to the liver, it is obviously a very life-threatening situation. There are some cancers that tend to spread preferentially to the liver. Things like colorectal cancer will frequently spread to the liver and only to the liver, and neuro-endrocrine cancers will do that, and other gastro-intestinal cancers will do that, so it is an organ that is a common target for cancers. It’s also an organ that is critically important to the patient’s survival. Many patients die of liver metastases, and if there is a way to control those liver metastases, even if they have minor areas of other tumors in other places, that will extend their life and give them more opportunities.
Was this an area that was in pretty dire need of a solution to at least increase these responses to treatment because a diagnosis of metastatic melanoma or other metastatic cancer to the liver was pretty grim?
Dr. Faries: It was. Many of the patients that we see in the melanoma trial have melanomas that started in their eye, which is relatively an uncommon type of melanoma but has this tendency to spread to the liver very specifically. Unfortunately, there’s been very little that’s been able to be done for those patients over the years. Most of the time, those patients, even after they’ve had the melanoma in the eye, essentially don’t get any follow up. The rationale for that has been that there’s nothing we can do for them if they develop metastases, so why should we look? Unfortunately, that means that many of the patients that we see with that type of melanoma, by the time they present, by the time their melanoma has been detected in the liver, it’s extremely advanced, and they have weeks to maybe a few months to live. There’s been very little that’s been able to be done for them.
How does the PHP process work?
Dr. Faries: The procedure used to be a great big operation, one in which all of the blood vessels into and out of the liver were surgically isolated. It is a procedure that’s still used occasionally, but it’s been described as being two snips short of a liver transplant, so it was a big operation. The downside is that it could only really be done once, but what’s happened now is they’ve developed a way to perform this procedure using a purely radiology percutaneous minimally invasive approach. It uses a system of catheters to both the chemotherapy to the liver, as well as isolating the blood that’s coming out of the liver so that it can be then cleansed. The patient is asleep under general anesthesia for this. We place a set of three main catheters – one catheter goes into the hepatic artery, the blood vessel that brings blood directly into the liver, and that’s the catheter through which we give the chemotherapy. There’s a second catheter that is placed into the main vein, the large vein that lies directly behind the liver into which all of the blood from the liver drains. That catheter has two balloons on it – one balloon that goes above where those veins come in, and the other that goes below so that all of that blood is contained within that one segment of the larger vein, and then all of the blood that is draining from the liver passes out through that catheter outside of the body. It passes through a set of charcoal filters that remove the vast majority of the chemotherapy from the blood, and then that cleansed blood is given back through a third catheter that goes into the jugular vein in the neck. The chemotherapy is given over about half an hour, and then allows us to wash out from the liver for another half an hour, and then the patients are able to be woken up and moved to their hospital room.
Do patients stay in the hospital overnight for this procedure?
Dr. Faries: They do, because we’re working with arteries, and because the blood passes through these filters, the patients have to be anti-coagulated – the blood has to be thinned so that it doesn’t clot during the procedure. Their blood is very thin during the procedure, and afterward, they stay in the hospital so that we can reverse the anti-coagulation and then remove those catheters that we had placed for the procedure. They generally are in the hospital from the night before the procedure through the night after the procedure and often, one more night after that.
Do they have this procedure more than once or does it depend on how they respond?
Dr. Faries: It does depend on how they respond, but essentially, everyone that we’ve treated has had multiple procedures. We treat them as long as their tumors are responding, or at least have stopped growing in size. On average, patients have gotten around three treatments.
What have you seen in terms of results of this procedure in your patients?
Dr. Faries: It’s been very promising. We’ve seen patients who have had at worst, stability of disease, so their tumors which were growing when they started the treatment stopped growing, and usually for many months. We’ve also seen a lot of patients who have very, very advanced disease who’ve had tremendous responses and who have failed to respond to other previous treatments, but with this ability to concentrate the chemotherapy, we’ve really seen fantastic responses.
How exciting is this for you, as someone who deals with this every single day?
Dr. Faries: It is exciting, particularly given that we have not had so much luck in having great responses for this disease in the past. To be able to look forward to looking at scans on a patient who is coming in to be followed up is a nice thing.
Are the side effects substantially less with this procedure because you filter out the chemo before putting the blood back in the body?
Dr. Faries: The isolation of the blood supply to the liver and the filtering out of the chemotherapy have the advantage of concentrating the effect on the liver where we want it, and reducing the effect on the rest of the body, and that has two implications. One is that it means that we can use much more chemotherapy, and that’s the most important part of it – we can use enough chemotherapy to actually kill the tumor. The other advantage is that it spares the rest of the body much of the exposure. There are still side effects to the treatment. The bone marrow is suppressed by the bit of chemotherapy that gets into the rest of the circulation, so we have to follow the patient’s blood counts after the treatment is done for a few weeks. They go home and they generally perk right back up again after the treatment, and as soon as their blood counts come back up, they’re feeling pretty good.
How much higher is the concentration than the average treatment?
Dr. Faries: It’s close to ten times the amount.
What is the status of your patient, Chris Wilson?
Dr. Faries: Chris Wilson is a fantastic guy. He is a former Navy Top Gun pilot who has been dealing with his melanoma for some time. He initially enrolled in the trial after having tried some other therapies, and he actually was randomized. This is what’s called a randomized trial, which means that half of the patients get the profusion and half of the patients initially don’t get the profusion. One nice thing about the way the trial is set up is that patients who get the alternative treatment, which can be anything, can cross over. If their tumors continue to grow on whatever other treatment they’re getting, they can switch over at that point and get the profusion then. He had originally gotten assigned to the alternative treatment, demonstrated growth of his tumor on that after about six weeks, and then switched over to the profusion, and he’s had just a tremendous response since that time. It was striking to look at his scans from the time he originally enrolled in the trial and the growth of the tumors that happened even over a short period of time, and then see the dramatic reduction in the size of his tumors since that time. He still has some things that we can see on his scans, but it’s hard to know whether there’s any living tumor in that or not. Clearly, he’s had a very, very good response, and now we’ll keep an eye on him from this time and see if those tumors don’t continue to shrink gradually over time.
How much are tumors reduced?
Dr. Faries: It’s well over 50 percent. It sort of depends on how you measure it. If you measure it by the diameter or the volume or what have you, it’s well over 50 percent reduction. We also don’t know for sure how much of the things that we can see on his scan are actually living tumor anymore versus dead tumor or scar tissue.
He was told he may have only nine months to live?
Dr. Faries: Yes, and he’s done really fantastic. He’s felt generally well in between the treatments. At this point, his bone marrow has been suppressed by the repeated treatments and by the previous chemotherapy that he’d gotten before this trial, so we’re not going to profuse him, at least in the near term anymore. That doesn’t worry me too much because there’ve been quite a few patients who we’ve stopped perfusing for various reasons whose tumors did not then begin to regrow, at least not as long as we have been following them.
After treatment and this tumor stabilizes, is it just kind of a wait and monitor it situation?
Dr. Faries: We continue to treat them as long as we think that the cumulative effects on the bone marrow and how they’re feeling are not going to be too much that might then preclude them from getting other treatment in the future. After we’ve stopped perfusing, we follow them. One of the things that we will run into, even with tumors that in the past have only really shown signs in the liver, is it may begin to turn up in other places, so this may not be the final answer to all of the problems. We may have fixed one of the issues, prevented people from dying of liver failure and liver metastases, but they may end up showing other disease elsewhere, and that will require other types of treatment.
Who is the ideal candidate for this treatment?
Dr. Faries: The treatment is really a treatment for the liver and doesn’t treat anything else, so if the patients have a substantial amount of cancer in other parts of the body, just treating the liver won’t help them. It is also only available, at the moment, through clinical trials, and the trials are limited in the types of cancer that are being treated right now. The main one that is open in trials in a few sites around the country is melanoma. At the National Cancer Institute, they have another trial that is open for colorectal cancer and neuro-endocrine cancers and primary liver cancers, but until the treatment has been more thoroughly evaluated in those areas, it’s only going to be available on a fairly limited basis based on clinical trials. The hope, though, is that once these initial trials are complete, it will become an approved treatment, and then it will be easier for patients with melanoma and potentially with other cancers to be able to be treated with it.
Is it possible down the road that the washing away of chemo could actually work for other cancer?
Dr. Faries: In addition to melanoma, there are other cancers that favor the liver as a site to spread to, and that is frequently the cause of death for those patients. It’s, cancers like colorectal cancer, neuro-endocrine cancer, and primary liver cancer, so this same strategy of treating the liver with a very focused, high dose of chemotherapy may very well prove to be effective in those cancers as well down the road. It certainly is a technique that can be used for other indications with different types of treatments, different types of chemotherapies, so that we may be able to see this benefit not just from melanoma, but from other cancers as well.
The importance of treating the liver is that the liver is such a critical organ for our survival, and the way the blood vessels are set up in the liver allows us to isolate that blood, and therefore isolate the chemotherapy and increase the effectiveness of the treatment. Whether this same thing could be done in other organs, isolating the blood flow to the other organs, it’s a thought, it’s a possibility. Isolated profusion has been used for many years in melanoma that has spread or that is affecting one limb – one arm, one leg. The blood flow to that leg then is isolated and we give very high doses of chemotherapy that way, so it is a concept that can be used in multiple settings. The innovation of this trial is the ability to do it in a non-invasive way and a way that can be repeated time and again.
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