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Neoadjuvant and Adjuvant Therapy in Metastatic Colorectal Cancer

Panelists:John L. Marshall, MD, Georgetown University Hospital;Tanios Bekaii-Saab, MD, Mayo Clinic;Cathy Eng, MD, FACP, MD Anderson Cancer Center;Daniel G. Haller, MD,FACP,FRCP, University of Pennsylvania;Tara E. Seery, MD, UC Irvine
Published Online: Tuesday, Aug 09, 2016



Transcript:

John L. Marshall, MD:
We’re going to come back to FOLFOX versus FOLFIRI. Is there anything that can help with what kind of regimens to use? We’ll come back to it; let’s talk about neoadjuvant for just a second. What do you see in a patient who’s resectable right now, synchronous—the patient I just told you about? There are 3 lesions—let’s make them all on the right—primary tumor in place, 52 years old. The patient says, “Get it out of me.” What are you going to tell him?

Cathy Eng, MD: It depends on how big those lesions are in the liver.

John L. Marshall, MD: One centimeter.

Cathy Eng, MD: All 3 are one centimeter?

John L. Marshall, MD: Three, 1-centimeter things, PET positives. Do we do surgery first?

Cathy Eng, MD: Sometimes we do surgery first.

Tara Seery, MD: We do combined surgery.

John L. Marshall, MD: How do you make up your mind?

Cathy Eng, MD: Well, once again, in all fairness, I talk to my surgeons.

John L. Marshall, MD: If they’re going on vacation soon or not?

Cathy Eng, MD: Sometimes they mark the area; they mark the lesions.

John L. Marshall, MD: Because it may go away.

Cathy Eng, MD: It may go away completely. That’s why I’m a bit hesitant if it’s only a centimeter.

John L. Marshall, MD: A lot of us have said we like to see the biological impact of that. We get to test the cancer.

Cathy Eng, MD: Because it’s likely you’re going to give them adjuvant chemotherapy afterward.

John L. Marshall, MD: There are some studies that said if you responded, you did better, right? Prognostically, it was sort of predictive. Does it guide you in a postoperative setting if you’ve given pre-op?

Tara E. Seery, MD: I think this is an area everyone has their own little niche.

John L. Marshall, MD: So, what do you do?

Tara E. Seery, MD: It depends on how much I gave beforehand. I usually always give something. It could be just Xeloda alone or maybe FOLFOX. What I have to remind people is to not give FOLFIRI if everything is resected. Sometimes, people will do that.

John L. Marshall, MD: Is the study positive or negative?

Daniel G. Haller, MD: Negative.

John L. Marshall, MD: Negative? This is the FOLFOX before and after resection. It’s 8% PFS at 3 years…

Tanios Bekaii-Saab, MD: It’s a negative study.

Daniel G. Haller, MD: With a positive conclusion.

Tanios Bekaii-Saab, MD: That’s a negative study, and actually that study is probably one of the main reasons why I am reluctant—for a patient who is a straightforward surgical candidate—to even give chemotherapy. Just go to surgery. For many of those patients, if they’re metachronous, a single lesion or a couple of lesions, I don’t even give chemotherapy after surgery.

John L. Marshall, MD: It’s really hard not to give that patient chemotherapy.

Tanios Bekaii-Saab, MD: I find it actually very easy after discussion.

John L. Marshall, MD: You must not be on an RVU (relative value unit) metric.

Tanios Bekaii-Saab, MD: No, I’m not, not anymore.

Daniel G. Haller, MD: An important part of that study is that whenever you have a baseline good result, it’s hard to show an improvement like with stage II colon cancer. In that study, they had to have 1 to 3 resectable lesions, and 50% only had a solitary lesion. So, they did so well that you couldn’t show a benefit.

Cathy Eng, MD: I agree with you on that.

Daniel G. Haller, MD: And that’s the problem.

Tanios Bekaii-Saab, MD: Because there’s probably no benefit in that group of patients.

Daniel G. Haller, MD: Correct.

Cathy Eng, MD: That was a select patient population.

John L. Marshall, MD: The main point I want to make is that I don’t know what to do with the stage IV, no evidence of disease patient. Am I giving adjuvant therapy? How much do I give? What drugs do I give? Biologics or not? Pre versus post? You make a decision based on your gut feeling, your multidisciplinary tumor board, and the surgeon’s vacation time, right? Let’s be honest; that’s true. Does anybody have science they can put in here other than the feel and experience?

Daniel G. Haller, MD: It’s experience. I think if someone has a solitary lesion or two lesions, they’re 4 years out, and they had a stage II tumor to begin with, not with 15 positive nodes, but with a lesser likelihood of extrahepatic metastases—I wouldn’t do anything. If they had stage III disease, N2, 5 lesions in the liver, there are no data on it. But, I would probably give them postoperative therapy.

Tanios Bekaii-Saab, MD: I agree, that’s a different disease. That’s probably a true bona fide stage IV with more wide metastatic disease.

John L. Marshall, MD: I think we’ve stopped doing this for the most part, but let’s say a stage III adjuvant got FOLFOX and a year-and-a-half later, the liver metastasis is resected. We’re not doing FOLFIRI, or are we?

Cathy Eng, MD: No.

John L. Marshall, MD: No? Maybe neoadjuvant, but not adjuvant FOLFIRI.

Cathy Eng, MD: No, definitely not.

Tanios Bekaii-Saab, MD: Depending on your intent, exactly. So, neoadjuvant has a different intent than adjuvant.

John L. Marshall, MD: Are you treating metastatic? Are you treating adjuvant?

Tanios Bekaii-Saab, MD: Absolutely.

Daniel G. Haller, MD: It was actually a negative postoperative trial of 5-FU versus FOLFIRI. It was small, but it was dead negative.

John L. Marshall, MD: But, no signal.

Daniel G. Haller, MD: No signal.

Cathy Eng, MD: It’s really important to emphasize that there aren’t enough trials really to look at the liver resection patient population.

John L. Marshall, MD: And it’s so hard to study because you’ve got patients with 5 liver lesions and some with 14 positive nodes who would be eligible, plus that one with isolated liver wedged off. They’re very different people, and you can’t really squeeze them into the same category. So, it’s clearly something we need to study.

Transcript Edited for Clarity

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Transcript:

John L. Marshall, MD:
We’re going to come back to FOLFOX versus FOLFIRI. Is there anything that can help with what kind of regimens to use? We’ll come back to it; let’s talk about neoadjuvant for just a second. What do you see in a patient who’s resectable right now, synchronous—the patient I just told you about? There are 3 lesions—let’s make them all on the right—primary tumor in place, 52 years old. The patient says, “Get it out of me.” What are you going to tell him?

Cathy Eng, MD: It depends on how big those lesions are in the liver.

John L. Marshall, MD: One centimeter.

Cathy Eng, MD: All 3 are one centimeter?

John L. Marshall, MD: Three, 1-centimeter things, PET positives. Do we do surgery first?

Cathy Eng, MD: Sometimes we do surgery first.

Tara Seery, MD: We do combined surgery.

John L. Marshall, MD: How do you make up your mind?

Cathy Eng, MD: Well, once again, in all fairness, I talk to my surgeons.

John L. Marshall, MD: If they’re going on vacation soon or not?

Cathy Eng, MD: Sometimes they mark the area; they mark the lesions.

John L. Marshall, MD: Because it may go away.

Cathy Eng, MD: It may go away completely. That’s why I’m a bit hesitant if it’s only a centimeter.

John L. Marshall, MD: A lot of us have said we like to see the biological impact of that. We get to test the cancer.

Cathy Eng, MD: Because it’s likely you’re going to give them adjuvant chemotherapy afterward.

John L. Marshall, MD: There are some studies that said if you responded, you did better, right? Prognostically, it was sort of predictive. Does it guide you in a postoperative setting if you’ve given pre-op?

Tara E. Seery, MD: I think this is an area everyone has their own little niche.

John L. Marshall, MD: So, what do you do?

Tara E. Seery, MD: It depends on how much I gave beforehand. I usually always give something. It could be just Xeloda alone or maybe FOLFOX. What I have to remind people is to not give FOLFIRI if everything is resected. Sometimes, people will do that.

John L. Marshall, MD: Is the study positive or negative?

Daniel G. Haller, MD: Negative.

John L. Marshall, MD: Negative? This is the FOLFOX before and after resection. It’s 8% PFS at 3 years…

Tanios Bekaii-Saab, MD: It’s a negative study.

Daniel G. Haller, MD: With a positive conclusion.

Tanios Bekaii-Saab, MD: That’s a negative study, and actually that study is probably one of the main reasons why I am reluctant—for a patient who is a straightforward surgical candidate—to even give chemotherapy. Just go to surgery. For many of those patients, if they’re metachronous, a single lesion or a couple of lesions, I don’t even give chemotherapy after surgery.

John L. Marshall, MD: It’s really hard not to give that patient chemotherapy.

Tanios Bekaii-Saab, MD: I find it actually very easy after discussion.

John L. Marshall, MD: You must not be on an RVU (relative value unit) metric.

Tanios Bekaii-Saab, MD: No, I’m not, not anymore.

Daniel G. Haller, MD: An important part of that study is that whenever you have a baseline good result, it’s hard to show an improvement like with stage II colon cancer. In that study, they had to have 1 to 3 resectable lesions, and 50% only had a solitary lesion. So, they did so well that you couldn’t show a benefit.

Cathy Eng, MD: I agree with you on that.

Daniel G. Haller, MD: And that’s the problem.

Tanios Bekaii-Saab, MD: Because there’s probably no benefit in that group of patients.

Daniel G. Haller, MD: Correct.

Cathy Eng, MD: That was a select patient population.

John L. Marshall, MD: The main point I want to make is that I don’t know what to do with the stage IV, no evidence of disease patient. Am I giving adjuvant therapy? How much do I give? What drugs do I give? Biologics or not? Pre versus post? You make a decision based on your gut feeling, your multidisciplinary tumor board, and the surgeon’s vacation time, right? Let’s be honest; that’s true. Does anybody have science they can put in here other than the feel and experience?

Daniel G. Haller, MD: It’s experience. I think if someone has a solitary lesion or two lesions, they’re 4 years out, and they had a stage II tumor to begin with, not with 15 positive nodes, but with a lesser likelihood of extrahepatic metastases—I wouldn’t do anything. If they had stage III disease, N2, 5 lesions in the liver, there are no data on it. But, I would probably give them postoperative therapy.

Tanios Bekaii-Saab, MD: I agree, that’s a different disease. That’s probably a true bona fide stage IV with more wide metastatic disease.

John L. Marshall, MD: I think we’ve stopped doing this for the most part, but let’s say a stage III adjuvant got FOLFOX and a year-and-a-half later, the liver metastasis is resected. We’re not doing FOLFIRI, or are we?

Cathy Eng, MD: No.

John L. Marshall, MD: No? Maybe neoadjuvant, but not adjuvant FOLFIRI.

Cathy Eng, MD: No, definitely not.

Tanios Bekaii-Saab, MD: Depending on your intent, exactly. So, neoadjuvant has a different intent than adjuvant.

John L. Marshall, MD: Are you treating metastatic? Are you treating adjuvant?

Tanios Bekaii-Saab, MD: Absolutely.

Daniel G. Haller, MD: It was actually a negative postoperative trial of 5-FU versus FOLFIRI. It was small, but it was dead negative.

John L. Marshall, MD: But, no signal.

Daniel G. Haller, MD: No signal.

Cathy Eng, MD: It’s really important to emphasize that there aren’t enough trials really to look at the liver resection patient population.

John L. Marshall, MD: And it’s so hard to study because you’ve got patients with 5 liver lesions and some with 14 positive nodes who would be eligible, plus that one with isolated liver wedged off. They’re very different people, and you can’t really squeeze them into the same category. So, it’s clearly something we need to study.

Transcript Edited for Clarity
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TitleExpiration DateCME Credits
Advances in the Treatment of Metastatic Colorectal CancerApr 01, 20171.0
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