Oral Therapies and Dose Reductions in MBC


Adam M. Brufsky, MD, PhD: The nice thing I like about oral therapy is the ability to adjust. Clearly, we all recognized, and most oncologists recognized, pretty quickly after the original stuff came out about the 2 weeks on, 1 week off regimen that it was overdosed. George, you know this better than me because you were the discussant, but my understanding is that they had to pick a dose that 5% of the United States would be able to metabolize. Is that what it was? Was that due to the metabolism of it or something?

George W. Sledge Jr., MD: Yes.

Adam M. Brufsky, MD, PhD: You were apparently overdosing 95% of the United States with the drug. Is that right, with capecitabine?

George W. Sledge Jr., MD:I do not remember the exact numbers, but it was something along those lines, yeah.

Adam M. Brufsky, MD, PhD: Yes. We all realized it pretty quickly, and we reduced the dose. Then Tiffany Traina, MD, at Memorial Sloan Kettering Cancer Center came out with a 1 week on, 1 week off regimen, and some of us use that. I use that, too. We do not know. I do not think that there has ever been any formal testing back and forth about whether that is as efficacious. We do not know, but we still use it anyway for the toxicity issue. That brings me back to tesetaxel, and then we will talk generally again. Were dose reductions allowed in the CONTESSA trial? Can you dose-reduce it?

Lee S. Schwartzberg, MD, FACP: Yes, absolutely. There were 2 dose reductions. There was a substantial minority of patients who had dose reductions in both the capecitabine and in tesetaxel. The capecitabine could be reduced pretty much once you saw anything, any grade 2 toxicity. To George's point, why are you doing the 2 drugs here? Let’s get it down for the toxicity. Yes, 27 mg/m2, which is the starting dose that was used, is a reasonable dose to start. As we gain more experience, there might be certain populations who can start a little lower.

Adam M. Brufsky, MD, PhD: That gets me to this point: when we get this to be a single agent, what a lot of us are going to do, especially in the elderly people for right or for wrong, is that we are going to dose-reduce quickly to avoid the use of growth factors. That is where I think this may go. I am trying to predict the future, and I may be wrong, but I suspect that a lot of people are going to start doing that. They are going to say, “Listen, I want to give this to you. It is an easy drug to take. It is 1 pill every 3 weeks. We are going to check your white blood cell count. Instead of giving you pegylated filgrastim or whatever, we will just dose-reduce you and try to treat you that way.” I do not know. Do you think that this is where this is probably going to go at some point? We do not know because it is so far in the future.

Lee S. Schwartzberg, MD, FACP: We will get some good experience with the monotherapy with a couple hundred more patients now at that dose, both those over 65 years of age and those below. Those will be helpful data.

Transcript Edited for Clarity

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