Treating Colorectal Cancer with Chemotherapy

Podcast Transcript

Scott Steele: Butts & Guts, a Cleveland Clinic podcast, exploring your digestive and surgical health from end to end.

Hi everybody, and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, the Chairman of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio.

Very happy today to discuss a topic that's near and dear to my heart. As many of you know, March is Colorectal Cancer Awareness Month. Colorectal cancer is either the number two or number three cause of cancer related deaths in the United States every year. However, advances in early detection and changes in treatment ultimately make it one of the most preventable and treatable forms of cancer. We're really excited to talk about this today.

It's my pleasure to introduce Dr. Smitha Krishnamurthi. She's a medical oncologist specializing in GI cancers here at Cleveland Clinic Taussig Cancer Center. She's an Associate Professor of Medicine at Cleveland Clinic's Lerner College of Medicine. Smitha, welcome to Butts & Guts.

Smitha Krishnamurthi: Thank you Scott. Delighted to be here.

Scott Steele: We always like to start out with all of our guests a little bit of background about yourself. Where you're from. Where did you train? How did it come to the point that you're here at the Cleveland Clinic?

Smitha Krishnamurthi: Oh, well, I'm originally, actually, I grew up in Cleveland, went to college here in Case [Western Reserve University]. But then I was gone for 11 years for my training in Philadelphia and Baltimore, and really as an intern in internal medicine. After spending some time on the inpatient oncology service, it was brutal. But when the experience was over, I realized that I had a great relationship with those patients and really love the science of oncology, so that led me to pursue the fellowship in oncology at Hopkins. Then I just happened to marry somebody who was from around here, and ended up back in Cleveland. Of course, delighted to be here at Cleveland Clinic working with fantastic colorectal surgery and surgeons such as you.

Scott Steele: Well, we're absolutely glad to have you here. Let's start with oncology. People hear that word a lot and they're going to see an oncologist and a chemo doctor, and there's a lot of different things out there. Just very briefly, what's an oncologist? How do you guys fit into this treatment paradigm?

Smitha Krishnamurthi: Yeah, we are one of the team that of doctors that patients may have. As a medical oncologist, I provide the drug therapy, chemotherapy, immunotherapy, targeted therapy, so we're frequently working with surgeons and radiation oncologists to deliver the total treatment.

Scott Steele: When patients meet with you, what point in their journey do they typically meet... Obviously it's a shock. Somebody comes along, they think they're relatively healthy, they get a symptom. Next thing, somebody uses the cancer word, and sometimes that's an incredible shock to patient's system. Where do you fit into play?

Smitha Krishnamurthi: So typically in my role as a treater of patients with colorectal cancer, they've found out their diagnosis often from a gastroenterologist, who's told them after the colonoscopy that it looks like cancer. Then usually would refer to someone like you, a colorectal surgeon. I'm usually not the first person discussing it. They've had time to get used to this idea, but they will come in usually full of worry about chemotherapy because of all the side effects it has. You want to right away find out what their concerns are. I think that first appointment is so important to provide the education. I think most people eventually find the treatment wasn't as bad as they thought it would be, and hope to allay those fears when we first meet.

Scott Steele: We're going to focus a lot on chemotherapy today. We'll go into some different types of medications that are treated. What is chemotherapy? How does it work? How does it attack cancer cells?

Smitha Krishnamurthi: Basically, all chemotherapy keeps cells from replicating. They may work in different ways, but they're going to be more effective against cells growing faster than normal like cancer cells. They do have collateral damage effects because other parts of our bodies are growing fast too, like bone marrow where we make blood, or the lining of our intestine, which is why chemo could cause diarrhea. Some of them will just prevent the cells from duplicating their DNA or prevent the cells from dividing. But bottom line, they're trying to kill cells that are growing fast.

Scott Steele: In terms of chemotherapy treatment, walk me through a patient comes to see you in your office. What can they expect during that initial evaluation then subsequent treatment sessions?

Smitha Krishnamurthi: Okay, so say we have a patient who's found out that they had a colon cancer. They've had surgery with you. It turned out that it had gone to the local lymph nodes, but hasn't spread anywhere else at stage three. So you refer the patient to see me because we know that chemotherapy cuts their risk of the cancer coming back in half.

When they come in, I want to, of course, find out what their concerns are. I want to find out about their medical history, what are their symptoms now, how active are they? That helps me to determine if they can tolerate chemotherapy, which type of chemotherapy.

At that point then, once you collected all that information through talking and I do a little exam, make sure their wound is healed well, look over their lab values, then we talk about the chemo options. What's the risk of the cancer coming back? Why would you want to consider chemotherapy? What do we expect the chemotherapy will do? What are the side effects. Help them make the decision.

Scott Steele: Let's break that down a little bit more. A lot of different people out there are probably... I get questions all the time. Do I have to have IV chemotherapy? Could I just take it in a pill? What about this whole staging thing that comes up? I hear you just used the word it goes to lymph nodes, stage three, but what if I have stage two? Do I need chemotherapy? There's a lot to unpack there. Let's first start off with just the pill form versus the IV form. How do you make that determination?

Smitha Krishnamurthi: For a long time, we had only one drug for colorectal cancer called 5-fluorouracil or 5-FU. It's literally been around for like 60 years. It's still the backbone of treatment for all gastrointestinal cancers. 5-FU can come in a pill form. The pill is called capecitabine, and when you swallow that, it gets converted into 5-FU in the body. We can swap out IV 5-FU for the pill.

However, another drug that we use usually only for stage three, some cases for stage two, is called oxaliplatin, and it's only available in IV form. If we're going to use that drug, that will have to be given through IV.

Scott Steele: Is there a difference in terms of the effectiveness of these medications, whether they're given through IV or a pill form?

Smitha Krishnamurthi: For the 5-FU, there's no difference between the IV or the pill, but a little bit different side effects. There's the convenience factor of taking a pill at home, but the pill form tends to cause more hand foot syndrome, like cracking, peeling palms and soles, a little bit more diarrhea.

Scott Steele: Let's jump back into the staging. You mentioned a little bit about the staging. Walk me through the staging just in very broad overview terms. Where does medical oncology fit for both colon cancer and for rectal cancer?

Smitha Krishnamurthi: Okay, for staging for the colon cancer, for example, it's pretty much cat scan, chest, abdomen, pelvis. Because this cancer spreads, if it's going to spread, most commonly to the liver. Then second place would be the lung. We'd like to see that that's been done. From surgery, we know whether it's spread to any lymph nodes. So those are the elements we look at, the tumor, the nodes, and metastasis, meaning the distance spread. If a tumor is confined to the colon and shallow, of course stage one. If it's involving the full thickness of the colon wall, but no lymph nodes, stage two. If it's gone to the lymph nodes, but nowhere else, stage three. If it has spread far away like liver, lungs, then that would be stage four.

Scott Steele: Where does the oncology in terms of giving them chemotherapy? In general, I know there's a lot of individualized therapy, but where does generally the patient get chemotherapy?

Smitha Krishnamurthi: Right. The beauty of colorectal cancer is that if it's caught early, it's quite curable with surgery alone, which is why screening is so important. I typically don't meet anyone who has stage one colorectal cancer. But for stage two patients, chemotherapy could help a few of them. It's a puzzle. We don't know why it doesn't work better, but it's estimated that maybe five out of 100 people would be cured by taking additional chemo after surgery for stage two. So we always recommend that our stage two patients meet the medical oncologist to hear about and decide if they want to do this. But it's optional.

Stage three though, that's where chemotherapy cuts the risk of cancer coming back in half. So even though a person could have excellent surgery, lots of lymph nodes taken out, all negative margins, we do know there's a risk of those patients having cancer coming back. By taking chemotherapy, that risk is cut in half. So we like to see everybody with stage three disease as well.

Then for patients who have stage four cancer where it spread, chemotherapy is given with the intention of trying to relieve any symptoms, help them live as long as possible, and sometimes to help people get to surgery, for example, for liver limited disease.

Scott Steele: For patients that have colon versus rectal cancer, is there a difference in the amount of time and the timing that you would give chemotherapy for these patients? Do you give it before surgery, after surgery? How long do these patients get this chemotherapy for?

Smitha Krishnamurthi: Yeah, so there is a difference. For colon cancer, they're typically going to surgery first, and then we are giving chemotherapy at six months of pill form if it's stage two, if the patient opts for that. For stage three, we have the options of three months versus six months depending on how many lymph nodes are involved, how bulky the tumor is. If it's not a really bulky tumor, it's not going the outer surface, not a lot of lymph nodes, a person could have just three months of the IV oxaliplatin, and either IV 5-FU, if you're a pill form, capecitabine.

Rectal cancer patients though, as you know, have a higher risk of the cancer coming back locally. If it's stage two or three, we're giving them chemotherapy pill form typically with radiation before surgery. Then we give them four months of the combination chemotherapy oxaliplatin with IV-5, if you're a pill, capecitabine. Now all of that before surgery typically. A little bit different sequence of events for them. But overall the treatment's not really longer in terms of the chemo part.

Scott Steele: I encourage everybody to go back and listen to one of the podcasts that we have with Dr. Sudha Amarnath, who guides us through the radiation type therapy. Let's play a little bit of game in terms of truth or myth. For colorectal cancer, when you give me chemotherapy, my hair is going to fall out.

Smitha Krishnamurthi: Oh well, great question because I think that is a huge concern for most patients because when hair comes out, it's just obvious to the world that you're on chemotherapy, you're sick. Really one of the better aspects of chemotherapy for colorectal cancer is that for capecitabine or 5-FU and oxaliplatin, it typically doesn't cause hair loss. For patients getting treatment for early stage disease or getting those drugs for advanced disease, that would be a myth that the hair would fall out.

Scott Steele: What are the typical side effects that are associated with chemotherapy?

Smitha Krishnamurthi: Our most common side effects are diarrhea actually. We're recommending a lot of Imodium and sometimes changing the diet around if that happens. 5-FU and oxaliplatin typically don't cause a lot of nausea, so most people are really relieved to hear that that's usually not a major toxicity. We also have much better nausea preventatives than we used to. Sometimes people have had a parent who had cancer 15 years ago, and they went through a very bad experience, and they're pleased to learn it's much better now.

 Scott Steele: I know you talked about three months, six months, but do they take it every day? Do they take it once a week? Is the injection different than the pill? How does this all work?

Smitha Krishnamurthi: Yeah, so great question. It's all outpatient chemotherapy, Say somebody's getting the oxaliplatin with the 5-FU, we call that FOLFOX. That is the most common regimen actually for colorectal cancer in the U.S., and it's given IV through a port. It's an IV going into a deep vein in the chest. It's completely implanted on the skin, and you don't have to take care of it and it's given every two weeks.

Patient comes in for treatment, gets their nausea medicines, gets the chemo in over a few hours, goes home, connected to the drug, 5-FU, which is running in through a pump through IV tubing into the port for two days. This is a part that really causes a lot of worry for people. Like, "What? I'm going to go home connected to this chemo for two days?"

It's definitely inconvenient. You've got this pump, and you put on the bed next to you at night, and you have to remember to reconnect around your waist when you want to get out of bed. But it's just two days out of every two weeks. So then that day three, come and get disconnected, free and clear to do what you like. So every two weeks for that regimen.

If someone's on just pill chemo, they're taking the pills twice a day, two weeks in a row, then one week off. Then I would typically see them every three weeks, get blood work, and meet to see, "How did it go? Did you have any bad side effects?" If so, the oncologist has to make dose adjustments. This has to be kept safe. We want to keep our patients out of the hospital. We don't want this to be miserable. That's why it's important to let the oncologist know if you're having any side effects in between the visits and to honestly report them at the visit.

Scott Steele: I know most patients could have side effects, but how many patients don't complete their chemotherapy? Is it a small percentage, or is it a large percentage out there that just can't get through this chemotherapy?

Smitha Krishnamurthi: Thankfully, it's a small percentage who can't get through. Say we're trying to get through six months of treatment for somebody who's got a lymph node positive stage three colon cancer, we can generally get through the six months of treatment. But the oxaliplatin drug that we use does cause a side effect of peripheral neuropathy, meaning numbness and tingling at fingers and toes. If it just kind of comes and goes, no big deal. If it's there more often than it's not, that's when I would drop that drug out. It's a toxicity that builds up. The more doses you get, the worse it is. Many patients maybe, oh 20%, are not getting all six months with oxaliplatin, but they're at least getting the 5-FU, which does most of the work.

Scott Steele: So back to truth or myth, the oncologist is only involved in a patient's care during the time that they get their chemotherapy.

Smitha Krishnamurthi: Oh, that's definitely a myth. That's one of the great aspects of my job is that we do end up becoming the coordinator of care for our patients, and we have long term relationships. Once the patients refer to an oncologist to start treatment after surgery, we do follow them typically for five years.

At the five year Mark for colorectal cancer, if there's been no sign of the cancer coming back, then we feel comfortable having that patient just follow up with their primary care doctor, and keep getting colonoscopies the rest of their life. But at least during that time when they're at risk for the cancer coming back, we are seeing them like every three months for the first two years, and every six months until it's been five years. So I really enjoy that getting to know my patients and their families.

Scott Steele: Smitha, one of the things that has made a lot of the lay press news over the last year is the increasing amount of young patients that develop colorectal cancer. Patients in their 20s doubled since the 1980s. Can you comment on this and tell the listening audience out there, why do you think we're seeing a higher number of younger patients getting diagnosed with colorectal cancer?

Smitha Krishnamurthi: Yeah, that is such an important question because, as you said, the rate has been doubling. Even we're seeing patients in their 20s having colorectal cancer, and most of these patients actually don't have an inherited condition. It's thought that it's something environmental. That's maybe something we're exposed to possibly in our diet, possibly elsewhere. But some of it could be linked to the obesity epidemic. But of course, Scott, you and I have had so many patients who are young and fit and then develop colorectal cancer. No clear reason why, like maybe no inherited cause, and of course they're not obese.

What can a person do? I think that until we know really what the cause is, I recommend to all my patients that try to eat food that's natural. If it has ingredients that we don't even know what they are, then it's best to keep that to a minimum. I think that's our best strategy is to have minimal processed foods.

Scott Steele: Yeah, I think it's critically important that we would both agree that if you have symptoms, pain, bleeding, changes in your bowel movements, weight loss, pelvic pressure that seems out of normal and is persistent, that's something you want to tell your doctor about. Then for everybody out there to make sure that you get appropriately screened. If you're scared of a colonoscopy, that is not a big deal. It's the number one way to catch this early, even at the pre-cancerous stage, so critically important.

Let's go back to what we were talking about before, that's chemotherapy, we use this thing. There's other medications that are out there to fight cancer. You mentioned radiation as one of them, but what is this immunotherapy? Is that chemotherapy on steroids or what? What is that all about?

Smitha Krishnamurthi: Immunotherapy has really revolutionized treatment for certain cancers like melanoma, and lung cancer, and a subset of colorectal cancer. It's basically a category of drugs that rev up your own immune system so that it can fight the cancer. So theoretically, if someone's immune system could fight the cancer, then even someone living with advanced widespread disease could potentially be cured. It's our goal to try to get immunotherapy to work for all patients with cancer.

Now for colorectal cancer, right now, the currently available immunotherapy works for people whose cancers have abnormal DNA mismatch repair. People might have Lynch syndrome, inherited type of colorectal cancer, or not Lynch syndrome, but their cancer has this abnormal DNA mismatch repair. For our patients with advanced colorectal cancer, that's unfortunately only a small percentage, maybe 3% who would benefit from the immunotherapy that's available now. But then there are lots of clinical trials looking at how do we tweak this immunotherapy to get to work for the other 97%. I know my patients are hugely interested in those kinds of studies, and it's really important that they get done.

Scott Steele: So for all the listeners out there, we're lucky enough to have Dr. Krishnamurthi here, who was involved in a lot of the national guidelines in terms of treatment strategies with NCCN and other ones. Smitha, give us a look into the future. What type of research is your team doing at Taussig Cancer Institute in terms of looking at colorectal cancer? Is there something that's on the rise or something that our patients can be looking forward to?

Smitha Krishnamurthi: For everyone who's living with advanced cancer, we're recommending that cancer be tested to see what genes are abnormal in it. We call that tumor genotyping. We're having that done for all of our patients with advanced colorectal cancer to try to personalize their care. Because the chemotherapy we've talked about, it's used for everyone with colorectal cancer. We really don't have tests to know that it works better in one patient or another. We wish we had those tests, but we don't have them.

Then there are other therapies that would affect certain genes that can be abnormal in the cancer. So we want to find out for each person, like what's abnormal in your cancer? For example, there is an oncogene, so gene that it's abnormally turned on. It causes the cells to grow out of control. It's called PI3 kinase. We have a trial here with a drug that targets that abnormality. That's what we're looking for when we get this tumor genotyping done. Do we have a study, does someone else have a study that would benefit our patients?

Scott Steele: That's fantastic stuff. And as we finish up here, we always like to end with our guests a couple of quick hitters. What's your favorite food?

Smitha Krishnamurthi: Oh, chicken curry.

Scott Steele: What's your favorite sport?

Smitha Krishnamurthi: I love to watch tennis.

Scott Steele: What is your favorite travel place that you've gone?

Smitha Krishnamurthi: I'd say Sydney. Australia.

Scott Steele: What's the last nonmedical book that you've read?

Smitha Krishnamurthi: Oh, I had the pleasure of reading Know My Name by Chanel Miller. It's a very powerful story, a memoir. I'm so proud of her for taking control of her narrative.

Scott Steele: Then finally, tell us something that you like about Cleveland, Ohio.

Smitha Krishnamurthi: Oh, I love Cleveland because there's so much to do here, and it's not overcrowded, and it's not too expensive, and everyone is so nice. Of course that's a generalism. But that's really my impression having lived away, having been on the East coast for 11 years, which I enjoyed. But when I moved back to Cleveland, I was overwhelmed by just the kindness of all my colleagues, everyone I worked with in the hospital.

Scott Steele: Couldn't agree with you more. Tell the listeners a final take home message regarding oncology, chemotherapy, and everything for colorectal cancer.

Smitha Krishnamurthi: I would say write down all your questions, bring support people with you, your family, friends to that first appointment. Because there's so much information, you want to make sure that you don't have to be stressed out about trying to remember everything. Don't be afraid to ask your oncologist questions. That's what we're here for.

Scott Steele: That's awesome. To learn more about colorectal cancer prevention and treatment, please visit ClevelandClinic.org/coloncancer. That's ClevelandClinic.org/coloncancer. For additional information or to schedule a colonoscopy, please call (216) 444-7000. That's (216) 444-7000. Smitha, thanks for joining us on Butts & Guts.

Smitha Krishnamurthi: Oh, it's been such a pleasure. Thanks for having me.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.