Cancer Treatment Trials

my name is mike pishvaian and i'm a physician at medstar georgetown university hospital. i consider myself to be a clinical translational oncologist, meaning that i do research and i do clinical trials forpatients with gastrointestinal cancers and one of my main goals is to bring newtreatment options for patients with gi cancer i am also the director of the phase 1experimental therapy clinical trials program. the part that i enjoy about my job is that ihave an expertise in this cancer. i have an expertise in the underlyingmolecular abnormalities - the changes of the biochemical level that probably feed andgrow this cancer. and we have the opportunity to bring newtargeted therapies to try and fight this

cancer in a more specific way.one of my philosophies is to try and fight with them as much as i can but also to helpthem be as comfortable as possible through the fight. and when i talk to patients. when have my first meeting with them, for those who do not have a curable cancer, what i sayis that there are two goals to our treatment. one is to help you live as long as possible.but, the other very important goal is to try and make sure that the time you have left isthe highest quality of life as possible. pancreatic cancer is a very challengingdisease that requires a lot of expertise. if i were a patient, i would want to be in acenter that sees a lot of pancreatic cancer patients and has a lot of experience in thetreatment of pancreatic cancer.

one of the benefits of coming to a centerlike georgetown, is that we take a team approach to fighting pancreatic cancer.we have the surgeons, the radiation oncologists, the medicaloncologists and even the radiologists to read the films are intimately involved inthe care of the patient and each patient gets discussed in a multidisciplinary or teamgroup setting to make sure we're all on the same page as to how best to fight apatient's cancer. we know, and there's very good data, thatfor surgery for pancreatic cancer, the best surgeons are at their centers, that do a lotof surgery. but that also applies to the oncologists that treat pancreatic cancerwith chemotherapy.

we develop an expertise in the treatment ofpancreatic cancer. we get an understanding of whatchemotherapies work best and most importantly because it is a very challenging disease,for which most standard therapies, don't work all that well. an academic center likemedstar georgetown, will give us the opportunity to do clinical trials thatexplore new therapies, new ways of fighting the cancer. in other words, just going withwhat is the standard regimen we know doesn't always work that well.and so, we would want to be able to have our patients push the envelope, explore newtreatment options and hopefully they are the patients that do have benefit from someof these new clinical trials.

gi cancers include everything from theesophagus, stomach, pancreas, small intestine, colon and liver - but within thatfield, because we have five gi oncologists at georgetown, i tend to focus on pancreaticcancers and also refractory colon cancers. refractory meaning that patients who havehad all standard treatment options, are there new treatment options for them.i do see a vast majority of pancreatic cancer patients here in georgetown as a medicaloncologist, we see pancreatic cancer patients at all stages of their disease. so pancreatic cancer is a cancer of thepancreas. the pancreas is an organ that primarily secretes hormones, both into thegut directly and then also into

the bloodstream. the vast majority ofcancers that develop in the pancreas are of the kind that secrete enzymes into thegut directly. they're called adenocarcinomas.there's about 45,000 patients a year in this country who are diagnosed withpancreatic cancer and about 95% of those are these pancreatic adenocarcinomas.the pancreas is an organ that sort of sits right in the middle of the abdomen,underneath the stomach and next to the small intestine and because it's a fairlysoft organ with nothing really nearby, cancers can develop there often withoutsymptoms until they've progressed to where they're often not treatable by surgery.

it is curable in a small number of patients.about 10-20% of patients who are diagnosed with pancreatic cancer have operable diseaseand we know that surgery is really the only way to cure a patient.as a medical oncologist i offer chemotherapy and my radiation oncology colleagues willoffer radiation therapy, to try to improve the chances of curing a patient.but ultimately, only patients who can have an operation to remove the cancer will bethose that are curable. and that's only about 10-20% at most of pancreatic cancerpatients. this is definitely something that we want toget more of a word out about pancreatic cancer. pancreatic cancer has a tendency tospread very early. when a surgeon goes in

to remove the cancer, he'll remove theprimary tumor, but what we're concerned about more are the seeds that may havespread away from the primary cancer and are looking to grow elsewhere - typically in theliver or in the abdominal cavity. those are the parts of the cancer that couldeventually kill a patient. chemotherapy is aimed at trying to killthose seeds that are sown and are trying to find a home elsewhere.so, the answer is yes for the most part. patients with pancreatic cancer, at allstages, even the very earliest stages of pancreatic cancer, we do offer chemotherapybecause it's been proven to increase the cure rate after surgery. even a half acentimeter tiny cancer that had no lymph node

involved, we still offer chemotherapy forthose patients. we still think it's the right thing to do because the reality is thestatistics are that even at the early stages, at stage 1a pancreatic cancer, which is theearliest stage, there's still at least a fifty percent chance that the patient willdie of that disease ultimately. radiation is more controversial in thetreatment of pancreatic cancer. we do tend to use it and use it as part ofour therapy, but in fact, radiation has been proven to prevent the cancer from comingback after surgery in the area where the pancreas was. what we call local recurrence.but actually radiation has never been proved to increase the cure rate.so it's a tough decision.

do we try and reduce the local recurrence?or do we focus more on the fact that it doesn't help cure more patients.in this country, most patients are referred for radiation therapy whereas ironically, ineurope most patients do not get radiation therapy and it's really a matterof the physicians as a group looking at the glass half empty or half full.here in the us we tend to focus on the decreased local occurrence and in europethey tend to focus on the lack of benefit to survival. but the short answer is we do often recommend radiation therapy. we tend to recommend it after thechemotherapy after surgery has been completed and if the patient hasn't had thecancer come back at the end of the chemo.

so cyberknife is a form of radiation.it's highly focused radiation therapy. because the pancreas sits right in themiddle of the abdomen there are a lot of important organs nearby - the stomach, theintestines. in standard radiation, we'll incorporate those normal organs in thetreatment and can cause a lot of side effects like nausea, vomiting, cramping.cyberknife is most effective in helping to avoid those toxicities side effects to thenormal organs because in the case where the surgeon has removed the primary cancer,there's no cancer there still, what the radiation oncologist wants to do is to treatthe field, treat the general area where the cancer was and so it's hard to pinpoint that,he or she would prefer to just create a box

around where the cancer was.so cyberknife can't and really probably shouldn't be used post operatively but it definitely does have a role that we've explored and done clinical trials on for patients who can't have their cancer removed so we do know for sure that chemotherapyhelps improve survival in patients who have had the cancer removed. so about six monthsof post operative chemotherapy improves the cure rate by as much as about 20-30%.in the patients who have radiation therapy after surgery, as i've mentioned before,there is a significantly decreased chance that the cancer will come back in the areawhere the cancer was - what we call local recurrence. although radiation really hasn'tbeen proved to improve survival overall.

because the statistics of pancreatic cancerare so daunting, as i had mentioned earlier, we do like to offer clinical trials forpatients with resected pancreatic cancer. really the way that we think of it is that,we know that most patient's cancer will recur even after chemotherapy.so what can we do to try and push the envelope? can we do additional ordifferent chemotherapies that will help increase the chances of killing or curingthose microscopic seeds that are sown? can we do things like harness the immunesystem to try and prevent the cancer from coming back or from growing?and so we have clinical trials that are addressing both of those issues.

so for patients with pancreatic cancer,because it is such a deadly disease, we would think that in most cases theywould want to do anything they can to try to prevent the cancer from coming back.we know that the standard therapy does help but there's still a lot of room forimprovement. so clinical trials are usually where that room for improvement can bemanifest and at centers where they have clinical trials, like medstar georgetownwhere we can try and hopefully improve the outcome of patients with pancreaticcancer. the reality is that most of these clinical trials - at least when we'retalking about the post operative setting, are not going to compromise the standard ofcare. they're going to try and add to the

standard of care. so no patient will besubjected to a purely experimental therapy when we already have something that doeswork. we're going to try and just make what we already know work better.one of the benefits of focusing on patients with locally advanced unresectable canceris that we have the opportunity to bring new therapies to patients with cancer.combine them with what, as i mentioned, standard therapies of chemo and radiation,and to take a look at the cancer before and after these new therapies.so we have had clinical trials where we have our gastroenterologists sample a tumor verysafely through endoscopy, and then give a treatment of interest and then sample againand see what the treatment does to the cancer

these kinds of clinical trials are going tohelp us learn a lot more about pancreatic cancer and how it responds to some of thesenewer targeted agents. as we've developed a method for effectivelysampling patients, learning about the cancer. the goal would be eventually to do morepersonalized therapy where we sample a patient's tumor, then subject it to sometests that help guide what therapies that patient should get and then treataccordingly. that's really the sort of ultimate goal ofpersonalized medicine for pancreatic cancer. so unfortunately reality of pancreaticcancer is that 80% of patients do not have an operable cancer. of that 80% about 20%have what we call locally advanced pancreatic

cancer where the cancer has not yet learnedto spread to other organs but it's involved with the local arteries and makes certainsurgery impossible. the other roughly 40-60% of patients alreadyhave cancer that has spread. even at the first time of diagnosis.so, talking about just the patients with the locally advanced disease - we do knowthat the combination of chemotherapy and radiation therapy, will help keep thosepatients alive longer. so we're there actually.we have clinical trials already ongoing for patients with, in this case, metastaticpancreatic cancer. so, for example, we have a trial forpatients whose cancer has spread,

they're not operable candidates but we takea sample of their tumor through a biopsy. we send their biopsy to a lab that tests anumber of different proteins and enzymes and according to the result, based on theresult, we will give them a combination of two chemotherapies that are tailored to whattheir cancer expresses. the name of the trial is molecular tailoredtherapy for pancreatic cancer. and it really is our first foray intopersonalized medicine for metastatic pancreatic cancer. so this is what i spend a lot of my timediscussing with my patients. because most patients have an unresectablepancreatic cancer, and often where it has

spread to other parts of the body. in thosecases, their only option for treating the cancer, to try and control the cancer ,is chemotherapy. there have been chemotherapy trials thathave been done dozens upon dozens of clinical trials that have been done in thelast 12-14 years. and we are finally, finally just starting to enter the era where we areactually making some real progress. prior to 2010 there was really no agent thatwas proven to increase survival over about six months.now we have for the first time a trial that shows that you can improve survival toas much as a year and actually hopefully that would be a platform on which we can addnewer target therapies and extend the

survival beyond a year which would bereally a major change for pancreatic cancer. for the most part, clinical trials use newtherapies either targeted agents or even new chemotherapies or even new ways toenhance the immune system to try and treat the cancer itself.and those trials will add these new treatment approaches to the standard of care to try tomake the standard of care better. in cases where the standard of care isn'treally very good, such as patients who have had the first round of chemotherapy and nowneed another option, what we call 'second line therapy' - then really thefield is more open to explore more experimental therapies. it is definitely ourgoal in medstar georgetown to try and have

at least one, if not two or three clinicaltrials for patients at every stage of their cancer. that means for patients who have hadsurgery already. for patients that have had inoperable disease that has not spread.for patients who've metastatic disease, that means disease that has spread to other partsof the body, but have not yet had chemotherapy.and then even for patients that have had the first standard chemotherapies and needadditional options. so clinical trials are important becausethey help us learn how to treat cancer. and so a patient who enrols in a clinicaltrial certainly is doing a service to the greater good where we learn about theircancer. but the reality is that any new

agent, any new treatment that's beenapproved has gone through a clinical trial and we're always hoping that for that onepatient the new treatment that they're on, works for them.and we wouldn't subject a patient if we didn't genuinely think or at leasthope that this new treatment was going to be the right one for them. i get a lot of questions from patients abouttheir immune system and how that plays a role in their cancer. so we know for surethat the immune system probably plays a surveillance role, meaning that to somedegree, the immune system probably helps to prevent the growth of certain cancers.once the cancer's developed, there probably

is some opportunity to harness the immunesystem to help fight the cancer. but that is very much unproven territory.there are certain cancers, particularly things like skin cancer, melanoma and kidneycancer where the immune system we know plays a major role even for patients whosecancer has spread. for pancreatic cancer, it's not as welldeveloped and we are certainly looking at clinical trial to help us to understandmore. so we do have clinical trials that ask that question: can we enhance the immunesystem to help it fight the cancer potentially in addition to chemotherapies.we use vaccines. occasionally we use drug virus injections and sometimes we just useother agents that rev up the immune system

to try and control the cancer and it'seffects on spreading. the immune system's been studied withregards to cancer for probably the last 30-40 years and we've learned a lotabout the immune system in general and immune regulation from all the studies incancer. but it's ability to be applied to treatment of cancer is still, i wouldn't sayin it's infancy, but certainly is early on. with pancreatic cancer i think there aregoing to be ways to harness the immune system that are very specific to the cancer.so for example we have studies right now where we inject patients with a vaccinethat's targeted at their cancer. at their abnormalities that their cancer presents tothe immune system. but, one thing that i do

get a lot of questions about is - is thereanything i can do to "boost" my immune system. and there are a lot of alternativetherapies that are believed to boost up the immune system. unfortunately, none of thosehave really been proven to help yet. so there are things that patients definitelyshould do - such like exercise, keep up a good healthy diet, although i really wantthem to keep their calories up even if they can't eat the healthiest diet. there's a lotof discussion about the role of sugar in patients who have cancer. and a lot ofpatients will tell me, well we know that cancer feeds on sugar. and that's a littlebit of a misunderstanding cause our whole body feeds on sugar. it's just a matter of,do we have too much sugar?

and there has been good studies recentlythat have shown that patients who have uncontrolled sugar levels, uncontrolledblood glucose levels, that their cancer treatment is probably less effective.so a diabetic with cancer probably should have their diabetes maximally controlled totry and keep their blood sugar levels within a normal range. however, for a patient inregards to their diet, there's no real proof that having a vanilla milkshake instead of agreen leafy diet helps improve their cancer care. there are a thousand good reasons tohave a good normal healthy diet that includes fruits and vegetables and i wouldalways encourage that, but i also want to make sure that the patient is able to eatand keep their calories up.

that's probably as important as avoiding the wrong foods. so there are a lot of vitamins that havebeen explored as cancer prevention. and a lot of them are very promising. wejust don't know for sure whether they help in the prevention of cancer.but what we do know is that there's no real proof that these vitamins help inthe treatment of cancer. and what i warn patients on is that thepurpose of a lot of these vitamins and antioxidants is to prevent the damage that'sdone from the environment to our normal cells that could lead to cancer. but whenwe're treating cancer, particularly when we're treating cancer with chemotherapy,that is intended to damage a cancer cell,

the last thing i would want to have happen,is for a patient to take high dose vitamins or high dose antioxidants that ironicallyend up protecting the cancer cell and preventing the damage of the chemotherapy tothe cancer cell. so i do tell my patients just take a single multivitamin. don't takehigh doses of any vitamins or any antioxidants while you're on chemotherapy. so pancreatic cancer, because it's locatedin the middle of the abdomen with no major organs nearby until cancer starts togrow, often is very asymptomatic. meaning there's no symptoms.and often what happens, that when a patient is diagnosed with pancreaticcancer and the physician starts asking

them the right questions, they realize, ohyeah i was having some vague abdominal pain for the past two three months, i washaving some fatigue and my appetite was down a little bit. so often the symptoms arevery, very vague. but generally speaking the symptoms are abdominal pain, often thatgoes through to the back. fatigue, tiredness and often can be overwhelming tiredness.loss of appetite - sensation of getting full very quickly. and then if the cancer blocksoff the bile duct, the drainage of the bile from the liver, then patients can also turnyellow or jaundiced. that's what we call it. there are many factors that make pancreaticcancer difficult to treat and to cure. one is the diagnosis itself. again, becauseit's a diagnosis that is made often when

the cancer has grown, and often even spreadto other parts of the body by the time any symptoms develop. then we know we're reallyjust treating to try and prevent the cancer from growing but we're not going tobe able to cure patients. so it's the cancer itself and how it growsin the organ. there's also molecular uniqueness to thecancer. pancreatic cancers are often very resistant to most standard chemotherapiesand for example, we know that for certain kinds of cancers, they'll respond tochemotherapy at a rate of 50-60-70% and for pancreatic cancer we're lucky ifit's 10-20%. and that's just the nature of the cancercells and is a very common thing to most

pancreatic cancers.now i do want to bring a silver lining to all this and i do think that we might beentering an era for the treatment of pancreatic cancer where were for coloncancer fifteen years ago. the survival for colon cancer fifteen yearsago was about what it is for pancreatic cancer today and yet in the last ten yearswe've made dramatic improvements as we've understood how better to treat coloncancer. and i think with the breakthrough where we've actually been able to improvesurvival for patients with incurable disease up to a year or more - that may bethe first large step in trying to get these patients to live with their incurabledisease for longer than they did before.

so one of the areas where i consider i bringsome expertise, is that i understand the molecular mechanisms of the cancer which means that i understand what drives cancers. i understand what is abnormal incancer cells as compared to normal cells. and because of that i also understand how wemight be able to target some of those abnormalities to make chemotherapy and othertreatments more effective. and so one of the things as a scientist andas a clinician that i can bring to patient care, is that i can take what we might learnin the lab and apply it directly to patients or take patient samples and take itback to the lab to learn more about patient's cancers with the ultimate goal oftrying to give them more personalized care

to treat their cancer in the right way atthe right time.