DR FUCHS: A 42-year-old dedicated athlete, a marathon runner who I met, presented with metastatic disease with both peritoneal and liver metastases and initially got FOLFOX/bevacizumab with about an 8-month duration of therapy, then got FOLFIRI/bevacizumab for about 4 months. She was KRAS mutant and at that point was not interested in clinical trials, so I offered her regorafenib at 160 mg. And within a very short amount of time the principal complaint was fatigue. She had some mucositis and actually also some skin toxicity, but the fatigue was profound. And she came back and said that she wasn’t sure she wanted to continue on anything at that point.
We lowered it to 120 mg. The fatigue was still difficult for her. Finally reduced it to 80 mg and now actually has gotten a CAT scan at 2 months and a CAT scan at 4 months with stable disease, and she remains on 80 mg with some but acceptable fatigue. But it was challenging for her.
DR LOVE: Do you have a sense that she’s derived a benefit from treatment? I know it’s kind of always hard to say.
DR FUCHS: She had progression before the regorafenib. And she’s 4 months into it with stable disease. So I think there is some benefit, but based on her experience and, frankly, the experience of many other patients that I’ve treated with regorafenib, the toxicity that I see is considerably greater than was reported in the CORRECT study.
DR LOVE: Again, kind of reminds me a little bit — I remember when capecitabine was introduced. I guess it was — what, around 2000? It was a while back. And everybody just hated it. And then we were like, “Wow! No alopecia, oral medication,” and really breast cancer, initially, I remember it was just very much of an issue. And now it’s utilized a lot, particularly in breast cancer. I think now that people have kind of gotten the dosing down. I’m kind of curious, Charlie, how would you approach a patient like this to get young, otherwise healthy lady, a patient in terms of dosing?
DR FUCHS: I’m starting to wonder whether starting at 160 makes sense anymore. And others at other centers have said to me, including one center told me that they now routinely start at 80 and escalate for patients who tolerate 80. And I’m contemplating something like that.