My Treatment Approach: Metastatic Colorectal Cancer - Episode 7

Dosing Strategies for Regorafenib for Patients With mCRC

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Chiara Cremolini, MD, PhD, discusses dosing strategies and the optimal management of adverse events with regorafenib for patients with mCRC.

Tanios S. Bekaii-Saab, MD: Gerald, going back to you. Thinking about regorafenib, we have certainly had challenges with the 160 mg dose, which came out of the CORRECT trial. It really challenged us in the clinic, with key toxicities very early and very severe for some patients. A couple of studies looked at different dosing strategies, ReDOS, which is published now, and then REARRANGE, which was presented and is about to be published. How do you think about the dosing strategies and the challenges that remain?

Gerald Prager, MD: The ReDOS study used a design with a rapid escalation of the dosage. Patients started with 80 mg in week 1, escalated to 120 mg in week 2. Then, for those with no severe adverse events, it went to 160 mg in week 3. This study really nicely demonstrated that you can quickly find an individual dosage for your patients, thereby preventing severe toxicity. Also, more patients went into cycle 3, which was the primary end point of this study. This was significant in favor of this experimental arm. I think the data from the ReDOS study were quickly implemented in the treatment concept in many Western centers. Also, what we are doing when we see new patients treated with regorafenib, we use this ReDOS escalation design, as we call it, and this is very much appreciated in our patients. What we do is, we see the patients after week 2, so when they’re already on 120 mg, and then we decide together whether to go to the full dose of 160 mg, or we stay on the 120 mg. When we find the individual dose, we use this same dose for the next cycles of treatment. So this concept is very useful, and I think it’s a standard. You can call it a standard in starting a treatment with regorafenib, and it was adopted by most of my colleagues.

Tanios S. Bekaii-Saab, MD: Wonderful. It makes sense, of course. That’s exclusively what we use. Chiara going back to you, still thinking about the toxicities of regorafenib specifically, the hand-foot syndrome reaction, diarrhea, and others. We just recently published a paper in The Oncologist that looked at—this was part of the ReDOS study—preemptive use of clobetasol, so a steroid cream. It did appear to help, regardless of the escalation strategy, it seemed to help with toning down the hand-foot syndrome reaction. We haven’t adopted this too widely, but any thoughts from you? Is this a strategy that you think about for some patients? In addition, of course, to their education.

Chiara Cremolini, MD, PhD: I think that each kind of measure that may prevent or help early to manage toxicity from regorafenib is highly welcome. I think that one of the most relevant barriers for the proper use of this drug in daily clinical practice is that, since this is a pill, it’s quite easy to tell patients, “Go home and take these pills.” No matter if it’s 2 pills per day, 80 mg, or 4 pills per day, 160 mg. The crucial point is to make the patient aware, well educated, and coming back to the hospital in the case of adverse events, and to proactively manage these kinds of adverse events. Otherwise, the management of the regorafenib therapy will be poor, and we will not be able to push the use of the drug as well as possible. Therefore, we risk compromising somehow the efficacy of this treatment option. Managing them early and hopefully preventing these adverse events through the use of these kind of creams is crucial to increase the adherence to the treatment. Also we shouldn’t leave patients alone while taking these chemotherapy-free pills because still they have a toxicity profile, and this needs to be carefully considered.

Transcript Edited for Clarity