Advances in the Treatment of Colorectal Cancer Webcast February 17, 2009 Cathy Eng, M.D. Introduction

Transcription

1 Advances in the Treatment of Colorectal Cancer Webcast February 17, 2009 Cathy Eng, M.D. Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. Anderson Cancer Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. Introduction Colorectal cancer is the second leading cancer killer in the United States, but it doesn't have to be that way if only people were screened. For people who develop colon cancer now there's a whole range of treatments and increasingly personalized treatment as you'll hear about at M. D. Anderson Cancer Center. It's all coming up next live on Patient Power. Hello and thank you for joining us once again on Patient Power. I'm Andrew Schorr broadcasting live from Seattle, Washington. But I was an M. D. Anderson patient in leukemia and got excellent care. Now, leukemia is not that common, but unfortunately an all too common cancer is colorectal cancer. As a matter of fact in 2008 in the United States there were 108,000 colon cancer diagnoses and 40,000 rectal, and all together the deaths that year, in 2008, 50,000. Now, that's very real to me when I think about the mortality from colon cancer. My mother, Ruth, died from colon cancer. She was diagnosed many years ago after she had pain and bleeding, didn't want to tell anybody. When she finally got to the doctor it had advanced to her liver, and while she did have chemotherapy and it controlled the cancer for a while, eventually that led to her demise. Now, the other story is my dad who very early on when they developed colonoscopy he would have colonoscopy. They'd find these precancerous polyps, they'd snip them out, and while he'd have other screening every year or two, it never developed into colon cancer, and that's what we want for you. So we'll be talking about prevention today, but also at M. D. Anderson the advances in the treatment of colorectal cancer when it is diagnosed. Susan s Story Now, both aspects of that, prevention and advanced treatment are tied up in a story of a woman I'd like you to meet, and that is Susan Taylor. Susan is 55 years old. She lives a couple hours up the road from Houston in Onalaska, Texas. She has two grown daughters, and she's got five grandchildren. But about a year ago, in February of 2008, she was diagnosed with what proved to be advanced colon cancer, and she's going through a lot of treatment at M. D. Anderson, and we're going to tell the story of how she got there. And even just today, every couple of weeks she goes down the road to Houston, has chemotherapy, but Susan wanted

2 so much to be part of this program tonight that she joins us just before she drives home back to Onalaska. So she's been in Houston today. Susan Taylor, thank you so much for joining us. Thank you, Andrew, for inviting me. I appreciate it. So, Susan, I've been through chemotherapy, and those days can be tough and tiring. How are you doing right now? Actually I am doing very well. I've been on treatment, as you mentioned, for about a year, and it has really proved to be a lot easier than I thought it was going to be and I think largely because so many advances have been made through the years for the chemotherapy drugs. And I have really been very blessed to have a very I wouldn't say easy time but not nearly as bad as I thought it would be. Susan, I said at the outset that there's a message about prevention and screening in your story too, and colon cancer largely is a preventable illness if it's caught early, like at the time that we might have those precancerous polyps that many people can really develop over years. You don't feel anything, you don't know unless you're screened. Now, I know one of the guidelines is to have colonoscopy at age 50 unless you have family history or other symptoms. You weren't having colonoscopy. I think you didn't even have a mammogram. Why were you avoiding going to the doctor? Well, I think largely because I was just afraid. I was always afraid that somehow I would be one of the ones to have cancer, and I figured if I didn't know then I wouldn't have it. And how foolish that was. I did not have a colonoscopy. I should have. I had warning sign that I totally ignored, and if I had only paid attention at the time I wouldn't be in stage IV colon cancer at this point in my life. Susan, was there any history in your family that made you worry about cancer? Yes. My mother's mother had colon cancer in exactly the same area that I did, my mother's, every one of her brothers with the exception of one and all of her sisters died from cancer, different types of cancer but nonetheless cancer. 2

3 Now, I think you told me yesterday, we were chatting on the phone, you weigh about 101 pounds now. I think you're five foot one. That's correct. Tell me about your symptoms and your weight loss. Okay. February of 2008 I kind of began feeling almost like I had a slight flu virus or something. I was having a lot of diarrhea, and I was not feeling well. My energy level was really very low. I just didn't feel good. I thought perhaps I'd caught something from my grandchildren. So I just kind of ignored it and figured that it would eventually go away. And the diarrhea kind of turned into a kind of constipated diarrhea, and I just was having trouble. I couldn't go to the bathroom but I needed to go. It was just a really bad feeling. I began losing weight. Eventually I got down to about 79 pounds, and my husband said, oh, no, there is definitely something wrong. And he brought me to a hospital in San Antonio, urgent care, to get checked out. And that's how it all started. Now, you were checked out there. What happened? And then tell us about the journey that brought you to M. D. Anderson. Okay. I went to urgent care as I mentioned, and they did blood work. They scheduled a CT scan, and so I had "all of the above" done. I was also examined by the doctor on charge, and he actually felt around in my stomach area and felt a large mass, which I had never felt. And he was very concerned. At first he asked if I drank, and I said, no, I don't drink. And he was very concerned. So they did the CT scan the next morning, and I was told that I had multiple lesions throughout my abdomen. They encouraged me to meet with the GI facility there in San Antonio and to do it quickly. So the next week, the following week, as I was on the internet doing a lot of research to find out - I was just totally shocked. I just couldn't even believe that that was even for real. And I got on the internet and started checking out some information about hospitals and facilities for cancer, and I happened to notice that M. D. Anderson was rated the top cancer hospital in the country for the past several years. And how silly of me because I grew up or I spent a lot of time in Houston so I know of M. D. Anderson, but for some reason it didn't come to my mind right away. But when I saw it on the internet I knew that that was the place I needed to be. 3

4 So I called M. D. Anderson, talked with someone on the phone, and they were so kind and so helpful. I faxed over some information from the pathology report that I had received in San Antonio and immediately was scheduled to see the GYN oncologist. So two days later I was in Houston and having an exam. Thankfully, all of that came out okay. In other words the spread to female organs was clean? Yes. And so they reviewed the CT scan from the San Antonio hospital and determined that in fact the cancer had begun, originated in the colon and had spread to the liver. So they had an appointment for me the very next morning with the GI doctor, and that's how I got to M. D. Anderson. And I can tell you now that I am so thankful that that's where I wound up because the doctors are absolutely incredible. The information is shared back and forth between doctors, and you get absolutely the most attentive care. And it's very compassionate, which is important when you're facing something like cancer. Well, I found that too, and I came from a distance, had really hardly been to Texas, never been to Houston. And I know my wife and I when we went down there for first exams I went to Boot City because I thought that was where everybody went, you know, looking at boots. But Texas was new to me, but certainly the care and the warmth was like I was home folk, if you will. Now, you eventually had surgery, and then of course because the cancer had spread and was more advanced then you had what we call systemic therapy. That's what the doctors had, and that's been the chemotherapy and biologic therapy, we're going to learn about it in a minute, that's continued over the course of a year, right? That's correct. Yes. Okay. How are you doing? You go in for scans. How are you doing? What do they show? Well, as of this past October the tumors have been shrinking. When I first saw my CT scan from last April my liver was almost totally engulfed in tumors. When I had 4

5 my CAT scan in October you could actually see liver in between the tumors. I mean the tumors were actually shrinking, and I was just so excited, every reason for hope, every reason for optimism, every reason for cure. I had a CT scan in January, and the tumors are kind of stable right now. I'm still on the chemotherapy, and I will probably have another CAT scan in about a month or six weeks. Susan, we wish you well with that. Now, there's a whole team that supported you at M. D. Anderson, and there's a lot of the people in the team I like to talk about, these programs, you know, radiologists and pathologists, a lot of specialists that sometimes you never meet, but your medical oncologist who specializes in colon and rectal cancer is Dr. Cathy Eng, and she joins us now. She's had a long day in the clinic, and I want to thank her for staying late today. Dr. Eng is an associate professor in the department of gastrointestinal, or GI, medical oncology. Dr. Eng, so here is Susan, your patient who continues to undergo therapy but also continues to go about her life, and that seems encouraging, that people can have even advanced cancer and you can have therapies that can knock the cancer back. It seems like in many cases you do have that now. Definitely. Thank you, by the way, for having me for this event. Susan has been a wonderful patient. She's been very compliant and shows up for her appointments as scheduled, and she's just tolerated her chemotherapy extremely well, and we're very, very fortunate. Now, I've been watching this field for a little while, and certainly my mother having had it I started to learn about medicines as they've developed. The medicines have come a long way, but yet it's still when cancer advances I know it's difficult to treat. Let's start with surgery. So surgery usually comes first, right? No. Or how does it work? Oh, that's changed. Surgery is recommended in the setting of early-stage disease for a cure, basically, but for a patient with stage IV advanced disease surgery may not be our first approach. 5

6 All right. Now, like in some cancers we've discussed on Patient Power you'll do systemic therapy to try to reduce the size of tumors and then do surgery, or sometimes do you just forego surgery? If the patient has potential for therapy for cure, yes, we may consider giving some systemic therapy beforehand in order to shrink the existing tumor, but as Susan stated earlier she had extensive disease, and so to proceed with surgery first would not have been her best option. That would have delayed her treatment further in some settings. Now, in her case she had symptoms, so we had to proceed with surgery first in her case. Each case is very individualized. It depends on the patient's symptoms. It depends upon if the patient has evidence of obstruction on a colonoscopy, and that's basically the way Susan presented so we wanted to make sure we addressed that first in her case. But once again every patient is extremely different, and there are some patients that we never even consider surgery because they don't have symptoms regarding where their primary tumor is but they have extensive disease elsewhere and we need to address that issue first. Colonoscopy All right. We're going to talk about that in a second. I just remembered that part of Susan's story. Susan, they tried to do colonoscopy, right, and you actually had a blockage so they needed to get at that, right? That's right. Yes, the sigmoid part of the colon was almost completely closed off. Just a word about colonoscopy, Dr. Eng. So colonoscopy is sort of the gold standard as far as screening. For instance in mammography, we know mammography misses some breast cancers. What about colonoscopy? How much can we rely on it? The sensitivity is very, very good in actuality. The sensitivity is probably close to 90, 95 percent, so it's an excellent study. And it's really the standard of care. It allows you to visualize the entire left and right side of the colon versus let's say a flexible sigmoidoscopy which would not allow you to see the right side of the colon. So a colonoscopy would be ideal. 6

7 Now, so colonoscopy then. Now, I mentioned at age 50, what are the symptoms of colon cancer or worries about colon cancer where maybe that screening and investigation should go on earlier? In some cases patients obviously may see a change in the sides of their stool, the frequency of their stool, urgency, abdominal cramping. They may have weight loss which would be a later stage. They may have night sweats, which would also be a later stage of presentation. And obviously if there's any evidence of blood in the stool that's very concerning, and that could be both early- and late-stage disease. What about family history? Where does that come into play? Family history is always important for any malignancy and especially in colon cancer because there are some syndromes that are diagnosed that are associated with colon cancer, but they in fact only represent a small minority of patients that are diagnosed. A majority of individuals develop sporadic colorectal cancer. Actually familial symptoms only represent about five to seven percent of all colon cancers. Polyps Okay. I was mentioning about these polyps. My understanding is that those turning into actual cancer that it could take years. What's our understanding of the development, how long it takes in most people to develop colon cancer? It's roughly about anywhere between five and ten years where the polyp can eventually develop additional changes. Once again a polyp is not a cancer but has potential to become cancerous, and that's why it's very important to get the colonoscopy completed so the those polyps are visualized and can be removed. So it takes about roughly five to ten years for development of a polyp to become cancerous. Now, when a polyp becomes cancerous, so it's I guess attached to the wall of the colon, so is a stage I colon cancer where it's just slightly invading the wall and then the stages go through until it's spread to other organs? 7

8 Well, the staging is dependent upon whether or not it's penetrated what we call muscularis, which is a layer of the intestine itself, and then of course if there's any lymph node involvement. And then stage IV is the generalization that applies to all patients with disease outside of the colon that may have spread to another organ site. We're going to take a little break, and when we come back, Dr. Eng, we're going to fire off some more questions for you as we learn about diagnosis, getting an accurate diagnosis, what's the stage, what's your situation, how do they do that at M. D. Anderson and then how you evaluate what treatments might be right. What are standard treatments now, what are treatments that are in research at M. D. Anderson. We'll be right back with much more of our live webcast. You can give us a call, Much more in our live webcast on colon cancer right after this. Exams for Diagnosis Thank you for joining us for our live webcast as we discuss advances in the treatment of colorectal cancer tonight with Dr. Cathy Eng. She is an associate professor in the department of gastrointestinal medical oncology at M. D. Anderson Cancer Center in Houston. Also we have with us Susan Taylor, who is her patient, who has advanced colon cancer. Susan, are you still with us there before you head home? I think she's been with us. Well, we'll try her again in a second. Susan went through chemotherapy today and she was describing earlier what she's gone through, and as you will hear later on she has a very, very upbeat attitude. Back to Dr. Eng. Dr. Eng, so when someone comes to M.D. Anderson what are the exams you do besides colonoscopy or if they have already had that to determine what the situation is with their colon cancer? When every new patient comes in obviously one of the things we want to know is the stage of tumor, so we do request that if the patient has had outside radiological studies completed such as a colonoscopy or a CT scan we have those reviewed, and if necessary we repeat them. Once again, it varies by the stage of the disease. If it's an early-stage patient we do get our surgeons involved early on. If it's a rectal cancer patient we also include the radiation oncologist, and it's really a multidisciplinary approach, meaning it's really a team effort. And even in Susan's case, once again she was originally thought to have ovarian involvement and that's why she was seen by the gynecology oncology department and then in fact was determined to have colorectal cancer and was then evaluated 8

9 by the colorectal surgeon, and because of her extensive disease they had requested my assistance for the remainder of her care. So we really try to make sure that the patient is our number one priority, and we try to get all the team players involved early on because that's really the best way to approach these patients. Dr. Eng, I know from my programs I've been learning a bit of science, and I know that not all tumors, even if they are in the same size, the same place, are alike. So how much of a difference does it make now what the biology of a person's cancer cells are? You know, it may vary depending on upon what we call the pathology, basically evaluating the biopsy samples, and there are various degrees of what we call differentiation. And some may be more aggressive tumors than others. That may also have an impact. Obviously the number of lymph nodes the patient may or may not have had removed surgically and how much of those were in fact involved with cancer may have an impact if it's an early-stage disease. And then of course depending upon where the degree of tumor involvement is and how much tumor involvement there is for the patient. In Ms. Taylor's case, Susan's case, the degree of the involvement, the liver, was what really determined where we were going with her therapy. All right. We have a lot of questions, Dr. Eng. A lot of people want to talk to you. I want to thank our friends at the Colon Cancer Alliance for helping put the word out. I want to mention the phone number again, Questions for Dr. Cathy Eng from M. D. Anderson. And if you want to send an , and many people have, send it to patientpower@mdanderson.org. Patientpower@mdanderson.org. Personalized Care and Testing One question before we take our first call, Dr. Eng, and that is I've seen you quoted from studies you've presented about tests that you now have to help determine whether certain biologic therapies might be right for a given patient. Usually we want to know, well, is this therapy the correct one, should we move forward with this, or I understand now there's a test that you've been involved in to determine whether a certain very expensive medicine may not be effective so why even go forward. Tell us a little bit about this personalized care and testing. One of the pivotal studies that have been conducted basically looked at something known as the KRAS mutation. The KRAS mutation may be present in anywhere from 40 to 60 percent of all colorectal patients, and there appears to be evidence 9

10 that if you have the mutation based upon not only single agent studies but also studies combined with chemotherapy that if you have the presence of this mutation you will not necessarily benefit from what we call anti-epidermal growth factor therapies, such as cetuximab and panitumumab, and those drugs are two of our three biologic therapies that are available. Cetuximab is currently approved for utilization as a single agent or in combination with chemotherapy, and panitumumab is also a very similar agent created by a different company that is currently approved as a single agent. And these biologic therapies obviously can be costly because there's many, many years of development. These are monoclonal antibodies, and they may have some toxicities, and this class of drugs basically results in about 80 to 85 percent of patients developing an acne-like rash, and that usually happens in most patients within three weeks. And obviously it can be debilitating and can affect your quality of life. And it also can cause inflammation of the nail beds and cracking underneath the nail bed, which can be uncomfortable too. So the identification of the KRAS mutation has basically demonstrated to us that those patients who have the mutation actually do not benefit from this class of agents, and it would not be of use to provide it to the patient because in fact it may actually cause increased toxicities for those patients that have the mutation that receive this class of agents. So that is one of the first predictive markers that we have in colorectal cancer. Okay. But the idea of course would be to spare people toxicities as you say in oncology. Toxicity and expense, and obviously if there is no benefit to the patient there should be no reason why we should provide it to the patient, and they should consider other therapies. Right. Right. If you're going to go down that road of systemic therapies you want it to be right for you. I do want to mention just very briefly that those class of drugs are currently only approved in the late stage, stage IV setting. So some people may think so why shouldn't I get tested for this, but once again if it's an early-stage patient this drug is not currently approved in that setting, and that's why we don't test those patients for the mutation. 10

11 Listener Questions Great point. All right. Mercedes has been holding patiently. I think I've got your name right on line three. Mercedes, is that correct? That is correct, and I'm excited. Thank you. Now, where do you live, Mercedes? I live in Texas, in Houston, and am living here for four years. I was diagnosed with breast cancer in 2002 in South America in Peru. Now, do you have colon cancer as well? I just want to know if there is any relationship because I had a colonoscopy at M. D. Anderson, and they found a polyp that was precancerous, and I was very scared. I also have tuberculosis which I know that it's not related to any cancer, but I would just like to know if there is any relationship, if I should be having screens earlier than five years because they found that on me and I'm already a cancer patient. Okay. Good question. Let's find out from Dr. Eng. Any connection, Dr. Eng? In actuality it's more than likely that you developed a polyp as the result of just spontaneous formation of the polyp, and there's no direct link. There used to be some studies earlier that suggested there may have been a link, but from what we understand now there is not a common factor to account for both of your cancers. Please keep in mind that both breast and colon cancer represent two of the top three cancers in women, and once again colon cancer is a very preventable cancer, and that's why we're aware that you must undergo colonoscopy. You did the right thing by undergoing colonoscopy, and it's not unusual that patients with other cancers with find that they have polyps. Once again this is a very, very common cancer, and I would just recommend that you do standard screening evaluations for follow-up. 11

12 Thank you very much. That's fantastic. Good question. I know a lot of people worry about that. We're going to take another quick break. When we come back we've got Paula who is holding from Dallas, I believe. And then we have a number of questions that have come in. We'll be back with Dr. Cathy Eng, an expert in colorectal cancer, a GI medical oncologist from M. D. Anderson. Stay with us as we continue our live webcast sponsored by M. D. Anderson Cancer Center. We're back live on our webcast sponsored by M. D. Anderson. Andrew Schorr here along with Dr. Cathy Eng, associate professor in the department of gastrointestinal medical oncology at M. D. Anderson Cancer Center, and her patient Susan Taylor. We have a call from Paula in Dallas/Fort Worth. Welcome, Paula. Where are you exactly? Are you in Dallas or are you in Fort Worth? Actually, I'm between the two by the airport, in Southlake. Okay. I've been at that airport many times. Are you living with colon cancer, with a diagnosis? I'm living with rectal cancer. Okay. And how long ago were you diagnosed, Paula? August. And treatment that you've had for that? I went through radiation and chemo, then surgery and now the standard chemo. Okay. And what chemo are you receiving? The 5-FU, the one that starts with an L. 12

13 Leucovorin I think you call it. Yeah. And the third one, it's the standard cocktail, they told me. Okay. Well, you have a question now. We can't practice medicine over the internet, but let's do our best to give you some guidance. What's your question for Dr. Eng? Okay. The cell I had was aggressive, but the pathology report was good because it was good clean margins. They took out my rectum and a third of my colon because we hadn't got the generic report back yet because I had a grandfather and a sister with the exact same tumor in the same place, and that report finally came back and said that it was negative for genetics, so that was strange. But anyway they took out 21 lymph nodes, and they were all fried so all we can do is say definitely a stage III so far because they haven't found any evidence of a stage IV, but we couldn't stage it beyond the III because so many lymph nodes were fried. But your question, Paula? My question is that my oncologist is considering only eight chemo treatments instead of the 12 that he discussed originally and my sister is going through. Is there any new reports or reason why we would do eight instead of 12? So I'm sorry, Paula, did you receive your chemo radiation therapy before your surgery? Yes. Okay. And so before you had your surgery did they suspect that you had maybe some lymph node involvement or no? Yeah. There were two lymph nodes that were rather large that showed up on the CAT scan. 13

14 Okay. And you said, if I'm correct, you said zero of those 21 lymph nodes are involved. Is that right? They couldn't test them really because they said they were fried from the radiation. Okay. So let me just clarify a couple of things. So basically, Andrew, what Paula underwent was what we call neoadjuvant chemoradiation therapy, which is the setting where you provide chemotherapy with radiation therapy up front to decrease the degree of tumor burden. This is now the standard of care for rectal cancer. So before she underwent her chemoradiation therapy it sounds like she either had a CT scan or what we call an endoscopic ultrasound which demonstrated that there was evidence of questionable lymph node involvement, so that would make her a stage III. But then after she completed her therapy, she now had zero of 21 lymph nodes that are positive, which is also very positive, and I think Paula has to keep that in mind. She went from a stage III to a stage II tumor. It's not because it was fried, it's because the chemotherapy and the radiation therapy worked, and that's the whole point of this treatment. We know that by providing the chemoradiation therapy up front before surgery rather than after surgery as it used to be, number one, patients are able to spare their sphincter, which is a very important part of quality of life, obviously. A lot of patients don't want to have a permanent ostomy. And number two is that basically we know that patients that receive this neoadjuvant chemoradiation therapy fare better by being able to tolerate their chemotherapy after their surgery better as well as have better local control. So in actuality everything that Paula underwent is very, very favorable because she went from what was believed to be stage III, received chemoradiation therapy, and in this setting chemotherapy is utilized to make the radiation more effective, and then she ended up with the stage II cancer. The reason, Paula, that you're receiving additional chemotherapy is because you were originally believed to be a stage III patient based upon those two lymph nodes that were noted to be enlarged, and because of that that's why you're receiving additional chemotherapy. Now, you asked a very good question. Your doctor is suggesting maybe only doing eight cycles versus 12 cycles, and what you're undergoing currently is what we call adjuvant chemotherapy, meaning that we're giving it to you after surgery to decrease your risk of recurrence. Your tumor has been removed so we now know that by giving you additional chemotherapy we're decreasing your risk of recurrence in the future. And the standard of care many, many, many years ago used to be to give you additional treatment for 12 months, and then we found out that 12 months was just as good as six months. And your doctor may be saying 14

15 only consider four months, which is eight cycles, because we know in fact the other, third drug, the cocktail that you're currently on I believe involves a drug called oxaliplatin, and oxaliplatin can cause a lot of side effects including neuropathy, which is the numbness and tingling in your fingertips and toes which can occur with prolonged treatments. Right. He keeps asking about my toes and fingers. Right. It causes two different types of that numbness and tingling, the neuropathy. One is attributed to cold sensitivity, and that goes away, but the more important one is the one that develops, that adds up over time the more treatments you receive, and it commonly occurs around cycle eight, and that's why he's considering that. Now, in actuality there is a trial in Italy, if I'm correct, that is ongoing looking at the benefits in colon cancer for in the adjuvant setting, so after surgery, in early-stage patients to decrease the risk of recurrence and whether or not three months is just as good as six months. But that trial is ongoing, and we don't have those results yet. So I think that's why he's considering a shorter time interval of chemotherapy for you. Paula, I'm just listening. It sounds pretty reasonable to me, so it's not a bad thing. I'm going to let you go. Okay. I hope that's been helpful. I know I've learned about it. And everybody wants to get the optimal anticancer benefit without having side effects that we have to live with. Neuropathy certainly can continue. We wish you all the best, Paula. Okay. Thank you. Dr. Eng, we got an in from Mia, and it relates to doing some radiation particularly on the liver besides chemotherapy or even before. And you can make sense of it. Here's what she writes in. She wanted to know your thoughts about what she calls cherry picking the tumors with optional radiation treatments instead of waiting for chemotherapy results. And she talks about something called the SIR-spheres for liver involvement treatment in conjunction with chemotherapy. 15

16 Could that show greater results? I wish I could talk to Mia because that would be a lot easier. I'm going the impression she has not received any systemic chemotherapy based upon that ? It's not clear, but I think she's saying, could you go after with some sort of targeted radiation even while you're waiting to see if the chemotherapy works and could that give you better results, combining the two. A good way to approach it would be systemic chemotherapy. That's what we would normally consider because our chemotherapy is quite effective nowadays. We have response rates anywhere from 45 to 65 percent depending on the study that you look at, so that's usually our first approach. To have some localized liver-directed therapy in conjunction with systemic chemotherapy is definitely being investigated at this time. Actually SIR-spheres is one way to approach that. It's basically not so well known, and it's not available at all institutions, but basically it is a way to basically provide local therapy, liver-directed therapy to the lesions, and it's definitely a potential option. I don't know if that would be my first approach, and actually at our institution we're still utilizing that as part of a chemotherapy protocol because it's still very early, not so much in development but in its investigation. Research and the Future Okay. We're going to take a break, and when we come back, Dr. Eng, we'd like to know for people such as Susan Taylor who are living with more advanced disease where research is headed because I know they hope that if they can keep knocking it back with drugs that are pretty effective are there others that can be very effective that are in development that you see coming down the road. We'll be back with much more of our live webcast with Dr. Cathy Eng and discussing advances in the treatment of colon and rectal cancer right after this. Continuing our discussion about advances in the treatment of colorectal cancer with Dr. Cathy Eng, associate professor in the department of GI medical oncology at M. D. Anderson, and also we'll hear from her patient, Susan Taylor, again in just a minute. So, Dr. Eng, M. D. Anderson is a research institution. I know I was in a phase II clinical trial, single center clinical trial for leukemia many years ago at M. D. Anderson, and often you have a discussion with people about the research you're doing. First of all, give us a window into where research is headed now for more advanced colon and rectal cancer. 16

17 As I mentioned earlier in the broadcast, the identification of the KRAS mutation has really changed our approach to our colorectal cancer patients. It's the first predictive marker that informs us whether or not a patient would benefit from anti-egfr, epidermal growth factor therapies such as panitumumab and cetuximab, so that is one of the first molecular markers we've been able to identify regarding specific therapies. And that's really just the first stepping stone for where we and many other investigators obviously intend to take the field. And we want to try to personalize the treatment as much as possible for each patient, and obviously I think it's going to get to the point where we're not just placing all colorectal cancer patients into one category just based upon their stage and treat them with one or two different regimens but actually based upon what their underlying tumor biology shows. So true personalized medicine. We hope. Obviously, that would be the best thing for the patients and hopefully decrease their toxicities and hopefully not have to give them therapies that they would not benefit from. Now, we mentioned along the way about family history. I mentioned my mom and my dad, and Paula was mentioning about other relatives of hers, but she said she had genetic testing but it was negative. So it get us worried when somebody else had it in the family. Maybe if that spurs us to have screening at the appropriate age that's a good thing, but if I heard you right before most of the time it is not a hereditary condition? Correct. That represents only a very small minority of patients, five to seven percent. Okay. Now, related to treatments, so we've talked about these monoclonal antibodies. So that doesn't mean that the traditional chemotherapies, like we keep hearing about this drug that's been around a long time, 5-FU, that's still very much a part of the combination care, isn't it? Correct. Actually it's been around 50 years as of last year, and it really remains the base of most of our therapies for colorectal cancer in both the early-stage and late-stage setting. 17

18 So is the idea that that hits the cancer cells one way and then these monoclonal antibodies, kind of cruise missiles, if you will, hit the cancer cells a different way, and then that has sort of a synergistic effect? Well, the biologic agents that you're discussing, we don't really consider them chemotherapy per se, meaning that 5-FU and irinotecan and oxaliplatin, those are what we consider standard chemotherapy agents, so they are not specifically directed to a particular target per se on the patient, whereas based upon what we understand currently at the time of drug development these certain biologic agents are usually targeting a particular pathway that's involved in colorectal cancer development. And so for instance as I mentioned earlier cetuximab and panitumumab, that targets the epidermal growth factor receptor pathway, whereas bevacizumab targets the vascular endothelial growth factor pathway, which is a very different pathway. And once again we only know so much. There are various pathways that are involved in colorectal cancer development, and some pathways involve other pathways or what we call cross talking, meaning that you think you're blocking just one part of it but in fact you may not be. There's much more involved than you realize, and the further we get along with understanding the drugs better, and with further treatment we understand the drugs a little bit more and we get a little bit more information, and sometimes what we think we understand we really don't. In some other advanced cancers, Doctor, I've done interviews with specialists where they're using PET scans to determine if the therapy is working. Do you use that in the GI cancers? We utilize PET scans when our CT scans may be not definitive or rather evasive and we have our suspicions that something else is going on. So PET scans can be quite helpful, but they're not usually our first selling point in regards to diagnosis for our colorectal cancer patient population. So it's really an accessory tool. Right. I'm just wondering, let's say if we're many weeks down the road and you're trying to assess how is it going, if they're on the right therapy, would you ever change course, if you will, based on some sort of exam like that? Sure. We do it all the time. Obviously if the patient is feeling well but regardless we still want to make sure that the treatment is working if they're an 18

19 advanced-stage patient, we tend to rescan them every two to three months depending on where they are in their treatment, and the whole point obviously is to make sure that nothing new has developed. And also we may obtain a scan earlier if the patient is not tolerating their treatment well and we want to make sure they should stay on that treatment, is it worth the effort? So, sure, we utilize our radiology studies all the time to help guide us. Dr. Eng, so you've devoted yourself to colon and rectal cancer. Are you hopeful? You're at a research institution. There are people listening who may have advanced disease, and as we know it can be very variable. Susan, I know, doesn't know what lies ahead. But you're involved at the very leading edge of research. How do you feel about things moving forward? I know there doesn't seem to be a magic bullet, but what encouragement can you give to people? I think it's important for people to realize that, first of all, it's important to keep in mind that with 5-FU alone which I mentioned earlier was really the only drug we had for several years, and it's 50 years old, patients, the median survival time for patients was 12 to 14 months, and now based upon the various regimens we do have and the combinations and more knowledge we have we're getting close to reportedly 32 months, which is a median. So once again I don't like to quote median survivals to the patient because every patient is different, and so although you may have a stage IV patient in front of you if they have surgically resectable cancer, meaning that their tumor can be removed whether it's metastasized to the liver or to the lung, their survival is extremely good. We're seeing reports of five-year survivals for liver resection patients anywhere from 35 to as high as 65 and sometimes 85 percent for single liver lesions. In fact I myself have a patient that's been with me since I started treated patients at M. D. Anderson, and he's been on therapy for his metastatic disease for over seven years. So every patient is extremely different, and I think it's important to keep in mind that although you may have a diagnosis of advanced-stage colon cancer it's not necessarily a death sentence. There are very good treatment options available, and because of the science that we have available a lot of these patients are being treated almost like a chronic disease. But I think the most important thing that we all want to do is try to cure our patients. Unfortunately if you're not a surgically resectable patient the five-year survival is quoted to be as low as less than 10 percent, and I think we need to work on that. Obviously there are exceptional patients that surpass it, but it would be very, very impressive obviously if we could increase those percentages for those patients. So we still have a lot of work to do, but we obviously are taking the field a whole different level further, and it's a very exciting time. 19

20 Dr. Eng, you're a relatively young specialist in colorectal cancer, so we wish you a long, long career, lots of breakthroughs along the way. And we want to thank you for your dedication to patients at M. D. Anderson and around the world for this broadcast. I know you started really early this morning in clinic and seeing many patients and then being with thousands of others tonight. Thank you so much for being with us, Dr. Cathy Eng, associate professor of GI oncology at M. D. Anderson. Thanks for being with us, Doctor. Thank you, Andrew. Advice to Patients from a Patient Now, I mentioned one of Dr. Eng's patients is Susan Taylor from Onalaska, Texas, and she's been listening to all of this and is an incredibly inspiring woman having just had chemotherapy today. Let's hear a little more from Susan. Susan Taylor, you've been listening to our discussion. You have had chemotherapy today. You've been going through it for a while and quite a journey. For somebody who is listening tonight where they or a family member was recently diagnosed with colon or rectal cancer what would you say? You've gone through it all, and they may feel a little hopeless at this point. I think the first thing I would tell them is don't feel hopeless. There is always hope. And I feel like M. D. Anderson is absolutely the place that I was meant to be, and I have been given so much by being at that facility, far more than I ever hoped or dreamed for. And honestly I probably should not even be here today, I should already be gone, but I know that there's hope out there because I have lived that hope. And even in the darkest hour, even in the darkest hour there's always hope. Don't ever give up. Just keep fighting. And if there are newer, better treatments that will develop for people even with advanced colon cancer do you think you will be hearing about them at M. D. Anderson? Absolutely. It is on the cutting edge. I cannot imagine being anyplace else. I want to be at a place, at a facility, a cancer facility because other hospitals do other things. They fix broken legs, they do heart surgery. I want to be in a place that 20

21 specializes in cancer treatment because that's what I have. And at M. D. Anderson you will always be on the cutting edge of any new research or development. It's an incredible place to be. Susan, you're on your way home back to Onalaska, and you've had treatment today, and I guess you'll be back in a couple weeks and you'll have more. What's your outlook day by day and for the future? Oh, day by day I live in the moment. I do the things I love to do. I garden. I read. When I get tired I rest. I visit family. And that really is my focus. That's my short-term and my long-term focus. I know that there's a possibility for a cure, but there's also equally an opportunity that there will be no cure, and so I have to do everything that I can do to live a full life, to love my family and to do things that are important to me. And that's what I do, and that's how I stay focused. Susan Taylor, we wish you all the best, a safe drive home from Houston, and we hope we can talk to you again and again and again and hear about other just wonderful days that you're having even with more advanced colon cancer and that hopefully there will be a cure some day. I agree. Thank you so much, and I appreciate your time. Wow. I love that woman, Susan. I know Dr. Eng does too. I want to thank everybody for joining us tonight on our discussion about colorectal cancer. We've covered a lot of ground. But remember there's a vast library of programs at. Take a look at our programs on genetics and cancer. Take a look at our programs about caregivers, a vital part of the treatment team. We'd love for you to check out those replays. Also, if you are in Houston remember to register for the Fourth Annual SCOPE Fun Run March 28, 2009 and sprint for colorectal oncology prevention and education, and go to mdanderson.org/scope. Thank you so much again for joining us. Lots of hope here. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all. Good night. Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. Anderson Cancer Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. 21