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WBEN NewsRadio 930>Audio & Video on Demand>>Melanoma Immunotherapies

Melanoma Immunotherapies

Mar 24, 2013|

A Roswell physician discusses Melanoma and Immunotherapies.

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Automatically Generated Transcript (may not be 100% accurate)

This is Roswell. Rookie by Roswell Park Cancer Institute. European opinion -- your total options. Your host him Wenger who welcome back to Roswell new instant comprehensive look at all aspects of future here treatment diagnosis and research. From a comprehensive source bronze -- -- cancer institute here in Buffalo, New York. Good morning I'm Tim later today immunotherapy. In melanoma treatment there is an awful lot of exciting. Things to talk about here in with us today to do that is doctor -- crucial -- associate professor of oncology in the section chief. Soft tissue and melanoma director. With CIO to program here at Roswell park doctor crucial money thanks for being here it's my pleasure thank you for having me got a lot going on with with your title in a lot to talk about today so. This this should be interest thing. Today focusing on on melanoma and in this exciting treatment. Few different aspects of treatment on let's start though with melanoma what is melanoma. Who should be concerned about it. Melanoma is a type of skin cancer. It is not the most common type of skin cancer and those are square in his cell and basal cell carcinoma or cancer of the skin. Melanoma is a type of skin cancer that arises from the -- -- sites these are cells that typically give the skin it's unique caller. So when we go out into the song on the final sites are stimulated. Days. Increase and they produce more -- in which is the pigment which in turn makes our skin darker and more canned. So people who are. Frequent sun worshippers who had frequent sunburns particularly during fare from growing -- -- -- and age young adulthood. And folks who have views down tanning salons and indoor tanning -- Those are patients who are higher risk for developing melanoma and what's really important here is that while there you know well it's not the most common. Skin cancers it is the most serious. Means you've already you know pointed out characterized. But he -- we shouldn't be lulled into. You know any kind of the sense of of comparability when it comes to skin cancer because. You don't know we need to be checked out I mean absolutely I could not agree more -- knoller remains the most fatal of the deadliest type of skin cancer. Because if it's high propensity to involve -- lymph nodes and metastasized or spread to other sites. On the common sites that melanoma can spread to include the long deliver the bone -- brain. -- and unfortunately there is still a rising incidence of melanoma particularly in white males. And there's been a progressive increase in the incidence of this disease over the past two to three decades. Approximately 9200. Cases. Of melanoma or expected to succumb to with this disease in 2012 based on estimates from the American cancer society's of this. Is continuing to increase. You are you mentioned some of the risk factors that feeling you know we're worried about handing you know sunburns -- that you set in the in the formative years. Fair skin and ultraviolet light moles. A lot of things a lot of different types of cancer should say under two other factors that that are key and in one would be the progression of age. On any other would be any kind of family history to those come to play at all with melanoma. On to some extent Tom melanoma however is a disease that can pretty march go across all age barriers I unfortunately have patients who are very young. My youngest patient was a team and I have patients who are elderly as well so we can pretty much just spam that's -- spectrum. Come in terms of family history there is suggestion that a family history of melanoma does increase. The risk for developing melanoma albeit small. Com and therefore these patients should certainly see dumber the logic ground surveillance and all the wars -- should be seen by dermatologists. For the full -- examination and periodic god timeframe are there every six months or at least annually. And and any time somebody sees that in mold that they've had for a long period of time has changed in characteristics and all the awards it has changed its collar. It has become larger suddenly or has started bleeding. Or increasingly if it has suddenly disappeared these are all concerning features and he should seek medical attention immediately. You know there's no good thing about any cancer but I guess the one is least positive thing about skin cancer and in even melanoma as that is it's an external it's something that can be observed. And so we really should the best screen I guess it's just personal observation you're absolutely correct -- so you really need to be aware of you know that any changes correct and your -- correct. -- you know we're gonna get into some specifics about different types of what we're about to talk about that when we hear the the phrase immunotherapy. Scary there amino what does that mean what does the phrase. The method of immunotherapy what is that the. Immunotherapy. -- is defined exactly as the word suggests immune. Being derived from the immune system of your own body and therapy in some form of treatment that's being offered. As opposed to chemotherapy -- meeting chemicals to some chemicals being administered into the body for. Treatment effect. The immune system that all of us have is primarily designed to recognize. Any foreign invaders. Putting it very simplistic -- And this is for infections or for cancer so if somebody has an abnormality. On the immune system gets activated and tries to fight this off. -- melanoma is one of those cancers which is believed to be one of the most immune -- cancers that we know about. That means he's expresses a vast variety of antigens which. Typically should be recognized by one's immune system but often is not and that allows this cancer to continue to spread and grow. This was. Defective immunotherapy may even be considered for melanoma Tom came out of observations that some patients with advanced melanoma. Actually have spontaneous regression of their tumors. Or as I described earlier. If somebody has a mole that has been present for a long period of time and that's -- disappears that's actually part of your immune system. Working towards. Trying to take that melanoma or that cancer deposit the way the second observation was that patients who have undergone an organ transplants such as a kidney transplant. They aren't immune suppressive medications to allow your body to. Except to the organ transplant those patience. People's immune systems are suppressed by these medications actually have a higher incidence of melanoma compared to the normal population. That these two observations made -- suggest that immunotherapy that means harnessing your own immune system to fight back against the cancer. Maybe a therapeutic strategy which in turn let tomb. -- wide investigation of immunotherapy and some of which have been dramatic success stories. When we talk about cancer we so often talk about surgery removal of -- tumors or in this case you know removal of melanoma. On chemotherapy as you've mentioned radiation treatments is immunotherapy in and of itself -- treatment or is it used in conjunction with any of the others and -- mentioned. It is used in both ways so melanoma when it is diagnosed in his early stages which typically meaning. Limited to the skin or possibly involving the lymph nodes is typically cut out surgically. Hums along as there's no evidence of metastatic disease -- spread to other organ systems. We consider following surgery we consider radiation on a case by case basis and we have specific guidelines for that. So each treatment decision is made at our center and it truly multi disciplinary fashion. Where each week comes the surgeons treating melanoma. Myself as a medical oncologist and the radiation oncologist. Lee apologists the radiologist all -- -- across and review imaging. Review deep apology. And then making a consensus treatment decisions all these patients. Immunotherapy such -- into -- can be used in the adjuvant setting which means after. Removal of the primary melanoma. If the melanoma stick or if it has involved lymph nodes. That is the indication specifically foreign -- on. On the other hand is if the melanoma has metastasized or involved other organ systems which we refer to it typically has stage four disease. Then immunotherapy can be used by itself as a definitive treatment option for these patients. You mentioned the test this is a few times here and that's you know when when -- cancer in this case melanoma spreads. Through lymph nodes or into other organs or or parts of the of the body. -- how common is that with melanoma. On the vast majority of patients who are diagnosed will likely not have metastasis. You know we diagnose upwards of 60000 new melanoma cases per year but the vast in the United States for the vast majority. Will be limited to the skin. It is the minority of patients that metastasized and that typically is a function. All the characteristics of the primary melanoma so we look into. How thick the melanoma is thick or thin. And this is a disease that I explained to our trainees and two patients sometimes life can be measured life and death being measured in a matter of millimeters. So the thicker the melanoma the greater the chance of this metastasized into love notes. If the melanoma is also rated which means the over lying skin covering up the primary melanoma is disrupted they have a higher risk. If something called my topic index as high which means when the pathologist looks under the microscope. He or she sees more cancer cells multiplying within a given square area. Those that patients are higher risk for -- -- season -- the lymph nodes are involved. Patients are at a very high risk for developing protester seized on the organ systems so we actually have Darius no programs in place where we plug in some of these numbers. So we can make act relatively accurate estimates of what the risk probability is. All spread to other organ systems or the disease coming back over the next five years. Hurry hurry to get into IL two in detail here in just a -- in a minute but one more thing on the test Assisi you know. We talked about early detection. You know is that chance that something is going to spread when it comes to melanoma. You know into the lymph nodes -- into an organ of the body. Is that. More prevalent the longer is to -- the leader in diagnosis that someone might be yours as early detection help I guess in. The answer is yes -- if one looks at stage one melanoma which is limited just to the skin and these are typically within melanoma is that we look at. The odds -- thought complete cure or are greater than 90%. With -- very early stage calls stage one -- beyond just pure as high as 97%. But as the melanoma becomes -- or the stage progressively increases the stage to Wednesday's three patients State's three meaning the lymph nodes are involved. The -- of -- -- progressively increase or the -- -- the cancer coming back over the next two to five years progressively increases okay now let's get into this immunotherapy into some some detail and I'll too I know is a big. That Europeans is a big part of it so let's say let's start by explaining them to me and everybody else would IL two is. So failed to is actually a naturally occurring political protein that all of us have within our system it's actually part of our immune system. Which is expressed by T cells TS and Tim Bjorn him. So express my T cells which are part of our immune system and these are essential for us to help off all ward off infection or any. Extraneous. Substances or -- infection cancer or anything else which typically gets activated. And therefore price to -- -- fight that off it. Now I failed to the original molecule was discovered back in 1975. And based on some seminal observations at the National Cancer Institute in preclinical models -- and all the awards in mouse studies. They found that administering high doses of loyal to. Actually made melanoma deposits or cancer deposits completely disappear which was very striking. So that in turn led to clinical trials. Four patients with advanced melanoma and the other indication for which it is FDA approved as advanced kidney cancer. Where's this was administered in very high doses intravenously. As a naturally occurring substance. And trying to primarily stimulate to harness your own immune system to fight back against the cancer cells in a -- it was trying to jump start your own immune system. And what if what they found was that a small percentage of patients. Actually had very very good responses where. All of their tumor disappeared which is quite remarkable in a solid tumor cancer. And in some of them on they have what was referred to as a partial response that means he shrinkage in the cancer burden. What was even more important was in many of these patients the responses -- durable. That means for example to paraphrase in chemotherapy we treat patients with chemotherapy. -- chemotherapy may work for awhile and after two or three months or 46 months the cancer becomes smarter and starts to grow again. We dial two in the small subset of patients the responses actually lasted for several years and our patience out there. Who have been treated with IO two over a decade or two ago. And have been completely cured of their disease. What sets these specific patients apart is still a matter effective investigation but this is. Very. Novel treatment that was originally FDA approved in 1998 for the treatment of advanced melanoma. Really is encouraging and this is Roswell this today and that is the voice of doctor Nikhil crucial irony here at Roswell park. An associate professor of oncology here and we're talking today about immunotherapy in melanoma treatment and specifically right now. Talking about this I failed to. Therapy that Roswell park has been quite aggressive and successful lift. Doctor crucial money -- this is you've characterizes and for everybody it is not for every patient with with melanoma how do we how do you determine. What patients. Our our -- prone to to respond to this. The -- administration a -- to pass to be restricted to centers of excellence that have that experience giving this drug. This is because this drug can cause significant toxicity. When used in -- in judicious fashion so we actually have to choose. In some ways the fittest of the fittest for this type of therapy because the -- carrier side effects including cardiac or heart side effects. Including drop in blood pressure or high fevers. Or chills and severe body shakes called riders. Kidney problems liver problems all of these unfortunately can occur with dial two. However when it is given inexperienced hands all of these talks to cities are very predictable. And they tend to be very short lived so home. We know how to administer this drug. And administering it can actually Ellis with some very good responses. So typically the screen a patient for eligibility trial true they have to have normal cardiac or heart function and we typically do -- stress test to reevaluate that. They also have to be. -- normal lung function we do something called pulmonary function tests so that's an ability our test of the ability of the long to. Function. And that is very very commonly done by all the knowledge is or lung specialists. And the third test that we will often we will always do is a scan of the brain to make sure that there are no metastasis -- spread of them don't know what to the brain. While the presence of metastasis is not an absolute contrary to occasion to use -- to we absolutely have to treat the brain metastasis first. Before we -- we weakens trial two of these patients. So in some ways this is. A treatment that is not for the faint hearted. -- we admit patients to the hospital for this on a typical. Case a patient is admitted on Monday morning. They get in -- -- this line that displaced into their neck and then at 2 o'clock in the afternoon they start there intravenous those -- to. This is given every eight hours for maximum fourteen doses. So theoretically be Friday night -- at 10 PM would be their last -- And barring any unforeseeable complications patient would go home on Saturday morning. They would then have a week off and come back in for the second cycle of an identical schedule. And then they get about six weeks off off to which we repeat their CT scans or their pet scans to determine what sort of response -- -- While there in the hospital they are placed on one of our cardiac monitor units so this is not the icu but many centers -- -- the country to put these patients in the icu. We have a -- of excellently trained nurses who take care of these patients. Who are very astute in recognizing. Or the early signs of side effects for these patients. And immediately call us the providers switches. Myself and the other physicians who do I'll to a Russell park and our mid level providers to nurse practitioners all the physician's assistant. Who. Take care of these patients on a daily basis in some ways. Mrs. The equivalent of having patience in the critical care all the icu like setting. Because they require so much medical attention before every single doses administered one of fuss is called. Two tell the nursing staff whether or not we can or cannot give that -- It is extremely rare for a patient to receive all fourteen noses the averages approximately nine to ten goes -- per cycle. What is the it's intravenous correct correct okay. What's the condition of the patient as they go through this process and I'm sure it varies because you've got this week on week off. You know we can and a six we collapse but if in general what is the condition of the patient mentally physically -- abilities. Very good question and that's where a lot of these support systems come into play that is both from our end as well as from the patience and almost invariably most patients will have a family member I just staying with them in the hospital or staying at two the hotel adjacent to Roswell park for the whole lodge. And -- that in my mind is very very important to help the patience to deal with the mental strain of being in the hospital. For that week. Most patients if not all will have some degree of toxicity. Or side effects in some patients will certainly have them more extreme compared to -- We do our very best in educating these patients beforehand what to potentially expect. But as you know every individual is different. And everyone has varying levels of side effects and varying levels of tolerance for side effects -- We in some ways hold their hands during this hospitalization. And become best of friends and patients who are admitted to. On the -- to service during that week if there are more than one patient which we frequently have -- often talk to each other in their hospital rooms. And friendships have been born through that as well because he may have someone in the hospital for the second course a -- to when you may have. A brand new novice for their first course of files to and it's not a infrequent that we see that an office asking for. Advice from the veteran who was already seen this before because once they've actually been exposed to it. They at least know what to expect the next time around. It's an aggressive treatment it's a tough treatment as you characterize it. But it is also works for -- may not work all the time but it works you know quite frequently in and and that's why you continue to do it here Russell park and you know. He just doesn't work right away -- mean. Obviously not because it's such a long process in England -- that we kind of -- coffins and then that the lakers it doesn't. Work right away and it again it is one of the down the basic tenets is that it tries to stimulate your immune system. To fight back against the foreign and radio which in this cases the cancer. So we typically takes about six to eight weeks for us to see any benefit if there is going to be a benefit and a 15% of patients where works. And that's the reason why we keep. Before a six week gap after the second week in the hospital before we repeat their -- you. It is not uncommon for -- to initially see a slight worsening of their disease you know on the first two or three weeks after treatment. Because dial two causes this unique site affect. Which in medical terms is referred to as the capital relief syndrome in simple terms it basically means that the blood vessels of the patient become more leaky. To think of it as a leaky garden hose and so all the water is basically going out through the holes of the garden -- -- as opposed to coming out at the other end it. The same thing happens with the -- to our blood vessels become very -- so. Most patients will have some degree of swelling so either in their legs. In their lower back and in extreme cases in their lungs and -- liver as well. Which is responsible for the side effects from this drug. These patients typically similar effects can actually occur in the areas with cancer so for example. If somebody has large lymph -- before we start their treatment. It is not uncommon in the first three to four weeks to actually see those live notes well because of -- units of the blood vessels that are supplying the lymph nodes. And then if they're destined to have a response shrink down over the period of six to eight weeks so the beauty of this treatment is that while it is very aggressive. We actually can predict what the potential side effects are and we can treat those side effects for the vast majority. And then within about eight weeks we will know whether or not a patient is going to respond or not to for patience to work clearly improved to a dial two. We bring them back for a second and then potentially a third and final course of treatment. Sold this requires a lot of commitment on the patient the patient as well as on the patient of the providers. For this aggressive form of treatment. The other. Part is that if a patient does not respond to that first cycle and a -- -- cancer. -- right through it we immediately know that this is not an effective treatments so we can switch them over to the other drugs that we now have available for melanoma. Which I'm actually very pleased to say we have much more now than we had you know two years ago. I'm sure it does not deter us from giving them additional treatment -- -- to did not work initially. Gonna ask you about taking this to the next level and you just kind of brushed on that. You know -- there's a clinical study underway right now to try to to help identify. Beforehand. -- you know who this will benefit. Yes this is something called the ideal to select study which Russell park. Is participating in conjunction with a national team called aside -- -- working group. On the side of -- working group is a group of investigators nationally. That has an interest in immunotherapy in cancers particularly from melanoma and kidney cancer. As we know oil to works in about 15% of patients. Which always begs the question how do we identify these patients or rather how to we spared the remaining 80% of patients. From the toxicity is a for drug that will not work for them. So in this clinical trial. We are actually collecting blood and tumor tissue samples this is from the original biopsies where the melanoma was diagnosed from. And then trying to examine these blood in tumor samples for genetic signatures that may help us predict which patients will and will not respond. This is a trial that is looking to -- approximately a 150 patients. And I believe we are roughly around a 120 patience recruit nationally so hopefully. By the end of this year or early 2014. We should have some preliminary results which may help us better streamlined individual treatment for patients. We've talked a lot about dial two and we don't have a ton of time left but we have enough time I think to brush on some of these other immune therapies that are available for. Patience of melanoma if you could -- address some of those forests sure as I mentioned earlier in de Ferran was a drug that was also approved in the late 1990s. For the treatment of melanoma that has already been cut out or receptive. And the intent there was to decrease the risk of recurrence in 2001. From march. The new drug -- new class of drugs. Called it feeling when -- was approved by the United States FDA for the treatment of advanced melanoma. Now if your little man has is also a form of immunotherapy. And unlike Kyle to is not administered in the hospital setting this as an outpatient form of treatment. It is given intravenously once every three weeks for a maximum four doses. And what if -- man tries to do again is tries to stimulate or in some ways over stimulate the immune system. To fight back against the cancer cells. Think -- fit as I thank you the example that all of us have a natural. Block to our immune system so if I get a cough or cold my immune system gets activated. But there are natural molecules that exist in my immune system to prevent or activation of the immune systems and so very well regulated cycle. Or think of it as driving a car you're on the accelerated of reducing the red light in front if you -- an analyst -- often needed to break. So if he works in a similar fashion where it tries to block that break in all the wars now you're free accelerators -- -- so it just simply tries to over stimulate your immune system to fight back and similar to royal -- About ten to 15% of patients can actually have a response to feeling -- And encouraging me a percentage of those can actually be long term responders. So we do have patience out there who have three to five years out from -- Palin moment. Which is also very very encouraging so. We have more now to offer patients and to we definitely have expanded the commentary. Finally doctor yeah yeah I know there's there's much more we talk about too but eating these are aggressive treatments as you very. Well laid out -- today. On and it's important that if anybody is is you know. Going to undergo them they do it at a place like Roswell park I mean these centers. Are prepared and trained to deliver this type of treatment. I agree on ideal tool is something that typically is done that senators like -- on people who man Barack can be very uncomfortably. Administered by community oncologists as well. And with -- If the patient. Recognizes any side effects from the drugs he or she should immediately contact their provider. Who can then. Initiate the appropriate treatment measures often steroids -- -- -- have been. So I think education and communication becomes. Paramount and then we have some new molecules that are coming up as well. The PD one antibody is one of those molecules though which is very very exciting it's it's similar type of molecule to get that little man. And Roswell park will have won -- the idea clinical trials which is going to test do you want a large number of patients we anticipate that'll open here in the next few weeks. Great take -- here today is that melanoma is a challenging disease but there are options and there's that there's a good deal of hope on that is absolutely correct you -- thank you so much -- crucial on the appreciated my pleasure thank you for having me that is doctor -- crucial -- here at Roswell park and associate professor of oncology section chief soft tissue and melanoma director. In the -- to program here at Roswell Park Cancer Institute in buffalo. If you'd like some more information you can always log on to the website Roswell park dot org. I -- some questions you'd like to ask personally can do so toll free at 1877. Ask our PCI. That's 87727577. To -- and listen to Roswell this Sunday mornings at 630 young WB yeah. -- by Roswell Park Cancer Institute your team opinion for your total options on line at Roswell this god of war. Hanging. And hanging do you. Then.

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