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Regorafenib in Colorectal Cancer: Optimizing the Dose

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: Thursday, Sep 08, 2016


Transcript:

John L. Marshall, MD:
When regorafenib (Stivarga) first came out, I was holding fast and true to 160 mg, four tablets, 21 days on, and 1 week off. I kept trying and I kept trying, and I really realized that I couldn’t get away with that because patients were stopping the medicine. So, what have you learned? You’ve been in practice the whole time this drug’s been out there. What have you learned about managing this drug?

Mohamed E. Salem, MD: I copy the same experience you had. When it came out, everybody was starting at 160 mg, because also it was a fear that if you decrease it, is it effective? But what I learned along the way is that most patients cannot tolerate that dose. And to your point, they actually stop the drug on their own. Even if you want to reintroduce a drug, sometimes they refuse. So, I think it’s very wise to start at a lower dose; 120 mg, I think, is reasonable, or even 80 mg is reasonable. But the key, also, is to bring them back very soon to check on them and give the supportive care, such as with the hand lotion.

John L. Marshall, MD: Hand-foot syndrome, fatigue, diarrhea, not a lot of liver function tests in my experience. But some, right?

Mohamed E. Salem, MD: Sometimes we see it. The problem is, if it gets missed, it can be fatal.

John L. Marshall, MD: Yes, don’t miss it.

Mohamed E. Salem, MD: Yes.

John L. Marshall, MD: As you’ve lived through this drug in our changing practice and all of that, what are some of the lessons you’ve learned?

Monica Chacha, RN: So, I’ve learned that the most important thing for patient compliance is to make sure that they understand the side effects and that they know how to deal with them. For example, nausea, how to deal with hand-foot, and to call us right away in case we have to decrease the dose a little bit or hold a week, something like that.

Mohamed E. Salem, MD: The study that got the drug to be approved is the CORRECT study, which was published by Dr. Grothey in Lancet Oncology in 2015. It was a randomized phase III trial, 2:1 randomization, which is standard design for a refractory setting patient. Half of the patients received regorafenib at the dose of 160 mg, 3 weeks on, 1 week off, on an every 4-week cycle. And the other arm received placebo because, at that time, there was no other standard of care.

The standard dose at that time was 160 mg. However, when we started to use the drug in the clinic, we started to realize some of the side effects at that dose, like fatigue, hypertension, hand-foot syndrome, and diarrhea. Because of that, there was a movement in the medical oncology community to investigate alternative doses or schedules. Most of us in the clinic use a lower dose to start with, such as 120 mg or even 80 mg, and a 3 weeks on, 1 week off cycle. And, in fact, there is an ongoing study now led by Dr. Axel Grothey and Tony Saab from Mayo Clinic, the ReDOS study, which is trying to answer that question.

John L. Marshall, MD: So, it’s not uncommon for us to change dose, whether it’s from three to two or up or down. Do I need a fresh script every time or do I just tell the patient the number of pills to take?

Monica Chacha, RN: I think it gets a little bit confusing because the pharmacy is going to go over the dosing with the patient before they ship the medication out. And then the patient is going to say, “No, I’m not supposed to be on that dose, I’m taking this,” and then they won’t fill it. Usually, you have to keep up to date on the prescription with what the patient is taking.

John L. Marshall, MD: Alright. We’ve learned a lot on how to dose this drug the best for our patients with metastatic colon cancer.

Transcript Edited for Clarity
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Transcript:

John L. Marshall, MD:
When regorafenib (Stivarga) first came out, I was holding fast and true to 160 mg, four tablets, 21 days on, and 1 week off. I kept trying and I kept trying, and I really realized that I couldn’t get away with that because patients were stopping the medicine. So, what have you learned? You’ve been in practice the whole time this drug’s been out there. What have you learned about managing this drug?

Mohamed E. Salem, MD: I copy the same experience you had. When it came out, everybody was starting at 160 mg, because also it was a fear that if you decrease it, is it effective? But what I learned along the way is that most patients cannot tolerate that dose. And to your point, they actually stop the drug on their own. Even if you want to reintroduce a drug, sometimes they refuse. So, I think it’s very wise to start at a lower dose; 120 mg, I think, is reasonable, or even 80 mg is reasonable. But the key, also, is to bring them back very soon to check on them and give the supportive care, such as with the hand lotion.

John L. Marshall, MD: Hand-foot syndrome, fatigue, diarrhea, not a lot of liver function tests in my experience. But some, right?

Mohamed E. Salem, MD: Sometimes we see it. The problem is, if it gets missed, it can be fatal.

John L. Marshall, MD: Yes, don’t miss it.

Mohamed E. Salem, MD: Yes.

John L. Marshall, MD: As you’ve lived through this drug in our changing practice and all of that, what are some of the lessons you’ve learned?

Monica Chacha, RN: So, I’ve learned that the most important thing for patient compliance is to make sure that they understand the side effects and that they know how to deal with them. For example, nausea, how to deal with hand-foot, and to call us right away in case we have to decrease the dose a little bit or hold a week, something like that.

Mohamed E. Salem, MD: The study that got the drug to be approved is the CORRECT study, which was published by Dr. Grothey in Lancet Oncology in 2015. It was a randomized phase III trial, 2:1 randomization, which is standard design for a refractory setting patient. Half of the patients received regorafenib at the dose of 160 mg, 3 weeks on, 1 week off, on an every 4-week cycle. And the other arm received placebo because, at that time, there was no other standard of care.

The standard dose at that time was 160 mg. However, when we started to use the drug in the clinic, we started to realize some of the side effects at that dose, like fatigue, hypertension, hand-foot syndrome, and diarrhea. Because of that, there was a movement in the medical oncology community to investigate alternative doses or schedules. Most of us in the clinic use a lower dose to start with, such as 120 mg or even 80 mg, and a 3 weeks on, 1 week off cycle. And, in fact, there is an ongoing study now led by Dr. Axel Grothey and Tony Saab from Mayo Clinic, the ReDOS study, which is trying to answer that question.

John L. Marshall, MD: So, it’s not uncommon for us to change dose, whether it’s from three to two or up or down. Do I need a fresh script every time or do I just tell the patient the number of pills to take?

Monica Chacha, RN: I think it gets a little bit confusing because the pharmacy is going to go over the dosing with the patient before they ship the medication out. And then the patient is going to say, “No, I’m not supposed to be on that dose, I’m taking this,” and then they won’t fill it. Usually, you have to keep up to date on the prescription with what the patient is taking.

John L. Marshall, MD: Alright. We’ve learned a lot on how to dose this drug the best for our patients with metastatic colon cancer.

Transcript Edited for Clarity
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