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Treatment Approach in Refractory Colorectal Cancer

Insights From:John L. Marshall, MD, Georgetown University Hospital;Mohamed E. Salem, MD, Georgetown University Hospital;Monica Chacha, RN, BSN, OCN, Georgetown University Hospital
Published: Monday, Aug 15, 2016


Transcript:

John L. Marshall, MD:
Like some of you out there, I’m an old oncologist. But, that means I’ve been around long enough to see the transformation in the management of metastatic colon cancer. When I started a long time ago, 20 years ago, the only medicine we had was 5-FU. Over the last one to two decades, a bunch of new medicines have come into play. And our ability to incorporate these medicines into the management of this disease has nearly tripled the overall survival for patients with metastatic disease. And, it becomes an intricate and interesting chess game that we play with all of the medicines.

Typically, we think of first-line therapy—fluoropyrimidine, 5-FU, or capecitabine, oxaliplatin or irinotecan—everybody has their favorite. And, then, we think of a biologic, depending on RAS status, whether that’s bevacizumab or one of the EGFR inhibitors. Then there’s this concept of maintenance therapy after that induction chemotherapy, where we can back off on the chemotherapy and extend first-line therapy even further, and minimize side effects. We then bring in second-line therapy. It was oxaliplatin to irinotecan, irinotecan to oxaliplatin. And, sometimes, we changed the biologic, sometimes we maintained the biologic. But, our strategy of intravenous chemotherapy combined with biologics has extended survival significantly.

But the news, of course, is that we now have agents that take us beyond first- and second-line into third-line. And there are many others on the horizon. Whether that’s around immunotherapy or novel molecular targeted therapies, these things are continuing to come, taking colon cancer from a really terrible acute disease to much more of a chronic disease. What we’re going to focus on in this piece is really about the refractory setting and the new medicines that are there, how those ‘chess pieces’ work, and how best to use them in your patients with refractory metastatic colon cancer.

So, now we’ve known this patient a while. They have metastatic colon cancer, they had frontline therapy, oxaliplatin-based therapy, and they usually have irinotecan-based therapy; biologics at this point. They’re now looking for what’s next. A refractory patient with metastatic colon cancer; we know this patient a lot. You’ve talked to them a thousand times, right? You know their families, kids, all of that, right? We have a sense of their social support. We come to the next decision. We’ve got two agents in the refractory setting. We have TAS-102 and we have regorafenib. How do you go about picking a patient, who’s the right one for what drug?

Mohamed E. Salem, MD: As you mentioned, after a while, the patient becomes part of your own family and you become part of their own family. And you know them very well. You even start to know their life, their kids, their wife, and vice versa. One of the important benefits of that is you can tell what’s important for them even without them saying that. As a clinician, one thing you want to make sure, aside from ‘Yes, your drug will work,’ is to make sure the side effects fit their lifestyle profile, especially in that kind of stage. They’re refractory, so they already received a rough treatment, as you mentioned. For example, if I have somebody who likes to play guitar, I might choose not to give him Stivarga because of the hand-foot syndrome that affects his lifestyle. I had a patient who actually was going to play in a concert, and that was a determining factor. If somebody kept having one infection after the other and had a low white cell or platelet count, I might shy away from using Lonsurf, because of the count problem. So, you have to tailor your therapy to what fits for that patient. In my opinion, I think colon cancer is a family name. I always think of every individual person as like a son and daughter, we share the same family. But, it’s different in its own character.

John L. Marshall, MD: I know, Monica, you have a lot of experience with both these drugs, managing it from the nursing side. Are there issues that distinguish where one patient you think might be better on Lonsurf, or one patient might be better with Stivarga?

Monica Chacha, RN: I think it’s like Dr. Salem said. A lot of times it comes down to side effects. But, there’s another thing, too, that makes me think the Lonsurf dosing is a little bit complicated.

John L. Marshall, MD: It is.

Monica Chacha, RN: So, we have some patients that really have trouble keeping track of oral agents. Sometimes it makes me a little nervous to think of them taking day 1 through 5, 8 through 12; are they going to remember that? Whereas, if they take regorafenib 3 weeks on, 1 week off, it’s easier to remember.

John L. Marshall, MD: Easier to remember. They’re both complicated. I couldn’t agree more. So, I’ve got a patient with hand-foot syndrome already, because I use a lot of capecitabine. That’s maybe going to sway me to use TAS-102. Whereas, if I’ve got somebody with significant myelosuppression, one of the things I like to make sure of is to not wait too long. Because, we have access to phase I trials and other kinds of treatment for patients. We try not to wait too long, one of the key elements I like to get with patient selection. 

Mohamed E. Salem, MD: I agree. And I also always say to my patient, you don’t have to have that drug or this drug as long as we have an option. That is the key to extend life, and do well.

John L. Marshall, MD: Yes, right.

Monica Chacha, RN: We have patients that are wondering a whole host of questions, especially since a lot of these patients have not been on oral therapies before. So, they’re asking me, is it okay for me to be taking this medication at home? They want to know what foods they’re able to eat. Are they able to take stool softeners along with it? Does pain medication interact with the medications that I’m on right now? What kind of foods do I need to eat? Because you can only eat low-fat diets around the time that you’re taking the medication.

John L. Marshall, MD: A lot of times, we tell patients about both of these medicines, or they’ve gone online, or some support group has told them. So, they know about both of them. And we do our best to try and inform them of the risks and benefits, and sometimes let them decide. They come down here and have a preference for one or the other. I know you’ve had that experience, and I know you’ve had that experience. And so, I do think that’s a reasonable strategy for some patients. In the right patient, give them enough information so that they can have a choice in this as well.

Transcript Edited for Clarity
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Transcript:

John L. Marshall, MD:
Like some of you out there, I’m an old oncologist. But, that means I’ve been around long enough to see the transformation in the management of metastatic colon cancer. When I started a long time ago, 20 years ago, the only medicine we had was 5-FU. Over the last one to two decades, a bunch of new medicines have come into play. And our ability to incorporate these medicines into the management of this disease has nearly tripled the overall survival for patients with metastatic disease. And, it becomes an intricate and interesting chess game that we play with all of the medicines.

Typically, we think of first-line therapy—fluoropyrimidine, 5-FU, or capecitabine, oxaliplatin or irinotecan—everybody has their favorite. And, then, we think of a biologic, depending on RAS status, whether that’s bevacizumab or one of the EGFR inhibitors. Then there’s this concept of maintenance therapy after that induction chemotherapy, where we can back off on the chemotherapy and extend first-line therapy even further, and minimize side effects. We then bring in second-line therapy. It was oxaliplatin to irinotecan, irinotecan to oxaliplatin. And, sometimes, we changed the biologic, sometimes we maintained the biologic. But, our strategy of intravenous chemotherapy combined with biologics has extended survival significantly.

But the news, of course, is that we now have agents that take us beyond first- and second-line into third-line. And there are many others on the horizon. Whether that’s around immunotherapy or novel molecular targeted therapies, these things are continuing to come, taking colon cancer from a really terrible acute disease to much more of a chronic disease. What we’re going to focus on in this piece is really about the refractory setting and the new medicines that are there, how those ‘chess pieces’ work, and how best to use them in your patients with refractory metastatic colon cancer.

So, now we’ve known this patient a while. They have metastatic colon cancer, they had frontline therapy, oxaliplatin-based therapy, and they usually have irinotecan-based therapy; biologics at this point. They’re now looking for what’s next. A refractory patient with metastatic colon cancer; we know this patient a lot. You’ve talked to them a thousand times, right? You know their families, kids, all of that, right? We have a sense of their social support. We come to the next decision. We’ve got two agents in the refractory setting. We have TAS-102 and we have regorafenib. How do you go about picking a patient, who’s the right one for what drug?

Mohamed E. Salem, MD: As you mentioned, after a while, the patient becomes part of your own family and you become part of their own family. And you know them very well. You even start to know their life, their kids, their wife, and vice versa. One of the important benefits of that is you can tell what’s important for them even without them saying that. As a clinician, one thing you want to make sure, aside from ‘Yes, your drug will work,’ is to make sure the side effects fit their lifestyle profile, especially in that kind of stage. They’re refractory, so they already received a rough treatment, as you mentioned. For example, if I have somebody who likes to play guitar, I might choose not to give him Stivarga because of the hand-foot syndrome that affects his lifestyle. I had a patient who actually was going to play in a concert, and that was a determining factor. If somebody kept having one infection after the other and had a low white cell or platelet count, I might shy away from using Lonsurf, because of the count problem. So, you have to tailor your therapy to what fits for that patient. In my opinion, I think colon cancer is a family name. I always think of every individual person as like a son and daughter, we share the same family. But, it’s different in its own character.

John L. Marshall, MD: I know, Monica, you have a lot of experience with both these drugs, managing it from the nursing side. Are there issues that distinguish where one patient you think might be better on Lonsurf, or one patient might be better with Stivarga?

Monica Chacha, RN: I think it’s like Dr. Salem said. A lot of times it comes down to side effects. But, there’s another thing, too, that makes me think the Lonsurf dosing is a little bit complicated.

John L. Marshall, MD: It is.

Monica Chacha, RN: So, we have some patients that really have trouble keeping track of oral agents. Sometimes it makes me a little nervous to think of them taking day 1 through 5, 8 through 12; are they going to remember that? Whereas, if they take regorafenib 3 weeks on, 1 week off, it’s easier to remember.

John L. Marshall, MD: Easier to remember. They’re both complicated. I couldn’t agree more. So, I’ve got a patient with hand-foot syndrome already, because I use a lot of capecitabine. That’s maybe going to sway me to use TAS-102. Whereas, if I’ve got somebody with significant myelosuppression, one of the things I like to make sure of is to not wait too long. Because, we have access to phase I trials and other kinds of treatment for patients. We try not to wait too long, one of the key elements I like to get with patient selection. 

Mohamed E. Salem, MD: I agree. And I also always say to my patient, you don’t have to have that drug or this drug as long as we have an option. That is the key to extend life, and do well.

John L. Marshall, MD: Yes, right.

Monica Chacha, RN: We have patients that are wondering a whole host of questions, especially since a lot of these patients have not been on oral therapies before. So, they’re asking me, is it okay for me to be taking this medication at home? They want to know what foods they’re able to eat. Are they able to take stool softeners along with it? Does pain medication interact with the medications that I’m on right now? What kind of foods do I need to eat? Because you can only eat low-fat diets around the time that you’re taking the medication.

John L. Marshall, MD: A lot of times, we tell patients about both of these medicines, or they’ve gone online, or some support group has told them. So, they know about both of them. And we do our best to try and inform them of the risks and benefits, and sometimes let them decide. They come down here and have a preference for one or the other. I know you’ve had that experience, and I know you’ve had that experience. And so, I do think that’s a reasonable strategy for some patients. In the right patient, give them enough information so that they can have a choice in this as well.

Transcript Edited for Clarity
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