INTERVIEW WITH DR. ROBERT LIVINGSTON

DR. LOVE: I'm curious to try to draw out a little bit more about your algorithm for metastatic breast cancer, given what I'm starting to pick up about your philosophy and the types of patients that you're seeing. What about the HER2-positive patient presenting with metastatic disease? What's your usual algorithm there?

DR. LIVINGSTON: Well, again, because of where we are, our usual algorithm is to offer that patient the anti-tubulin combination combined with Herceptin. That's part of the same study that we're doing, except of course, those patients get Herceptin added. All I can tell you about that right now is that it's very well tolerated. There doesn't seem to be any unusual or unexpected toxicity from adding the Herceptin to the anti-tubulin combination. I think that in the world outside of clinical trial, there are two very reasonable regimens to offer these people. One, of course, is Taxol and Herceptin, and the other is Navelbine and Herceptin. I'll admit to a certain bias, because of my previous involvement with Navelbine and my current involvement, but I think the Navelbine data are at least as impressive. I think that the combination of Navelbine and Herceptin probably ought to be used more especially if the patient is coming to you after prior exposure to a taxane in the adjuvant setting.

DR. LOVE: What about single-agent Herceptin?

DR. LIVINGSTON: You should never say never, but single-agent Herceptin is something that we only use in the context of a patient who isn't a candidate for chemotherapy or refuses chemotherapy, and especially if she's a candidate for hormone manipulation. So, for example, right now I have a patient, a young woman, who didn't want chemotherapy. She had a malignant, pleural effusion and a couple of other sites of asymptomatic disease, and had progressed after a couple of initial chemotherapy programs. We knew she was HER2/neu positive and that she was hormone-receptor positive. We actually did a PET scan with an estrogen label and showed that she still had the mechanism for concentrating estrogen in her tumor cells.

DR. LOVE: That's pretty cool.

DR. LIVINGSTON: Yeah, pretty cool.

DR. LOVE: How'd you do that?

DR. LIVINGSTON: I'll tell you about that. But, basically, the patient was placed on the combination of letrozole, Herceptin and pamidronate, because she had a couple of bone mets. She is now a year on this therapy with a good response. In fact, she's basically in a complete remission. So, there are settings where I think Herceptin is the only - I'm not sure you should call it a cytotoxic agent - but the only non-hormonal agent, non-hormonal systemic agent, that makes sense. But I think that we very seldom use Herceptin all by itself. I think there's usually some rational combination you can think of.

DR. LOVE: While we're talking about Herceptin, how long do you continue the Herceptin?

DR. LIVINGSTON: We usually continue Herceptin as long as the patient appears to be not progressing. And sometimes, we will continue the Herceptin beyond progression.

DR. LOVE: So, you continue it at least until progression?

DR. LIVINGSTON: Yes.

DR. LOVE: How do you determine whether to continue it beyond progression?

DR. LIVINGSTON: We don't know the answer.

DR. LOVE: The art of oncology?

DR. LIVINGSTON: Well, the truth is that I think practice varies among the three of us who do oncology in my institution, and only a randomized trial, which, as I understand, is now being instituted by Genentech is going to answer this question. Because we no longer have a situation where we're certain that continuation of that agent is fruitless, if you believe that the agent is working in part through potentiation of some other mechanism, then you have to have your mind open. For example there is the possibility that the Herceptin might potentiate Navelbine after Taxol.

DR. LOVE: Now, when you use a chemotherapeutic regimen plus Herceptin, at what point do you stop the chemotherapy and continue the Herceptin, or do you continue the chemotherapy at that point?

DR. LIVINGSTON: That's another very good question. And, again, I think it really depends a lot on individual practice, because there's no randomized trials to guide us. What I typically do is to treat the patient to what I think is a maximum response by anything that I can measure, assuming that she doesn't run into serious toxicity problems. Then I stop the chemotherapy and continue the Herceptin.

DR. LOVE: Hmm. What about the ER-positive, HER2-negative patient presenting for metastatic breast cancer?

DR. LIVINGSTON: Well, if they're ER-positive and HER2-negative and they do not have visceral-dominant disease, which many of them don't, we generally treat them with a hormone alone as the initial therapy, or a hormone plus a bisphosphonate, if they have bone metastases.

DR. LOVE: Now, when you say "if they don't have visceral disease," if they have, for example, a couple of lung metastases or a couple of liver metastases -

DR. LIVINGSTON: Lung metastases would not dissuade me. But, in general, liver metastases and peroneal metastases would dissuade me, based on the experience that was reported from years ago by people utilizing endocrine therapy. Those were so-called grave signs of disease. I have had patients who had relatively minor asymptomatic liver involvement, that I've treated with hormones alone and they've done fine. But I think, in general, liver involvement tells you that there's you, you're less likely to get a response and, if you get a response to hormone manipulation, it's likely to be short. But I don't think that's true of lung involvement. It's certainly not true of bone involvement. It's not true of skin or chest wall involvement.

DR. LOVE: So, for the patient, for example, who has visceral disease are you going to use chemotherapy or chemotherapy plus hormonal therapy?

DR. LIVINGSTON: Chemotherapy plus hormonal therapy, if we think that the patient is not a good candidate for hormones alone. Our typical chemotherapy would be CMF.

DR. LOVE: Hmm. Tell me about the PET scan estrogen thing.

DR. LIVINGSTON: PET scan estrogen. Well, this is an experimental study. The guy who's running the study is David Mankoff at my institution in nuclear medicine. There are two schools in the United States that have this study ongoing. Washington University in St. Louis is one, and the other is our institution, the University of Washington and the Fred Hutchinson Center. Basically, the concept is very similar to the concept of a glucose-PET scan, which I think everybody understands at this point. You positron label an estradiol molecule. You inject the estradiol into the patient, and only those sites that have the ability to selectively concentrate the estradiol - i.e., those with an active estrogen receptor - are going to take it up in sufficient quantity for you to see a hot spot in terms of PET admissions. There have been some preliminary presentations on this. I'm sure he hasn't yet published a manuscript. But our experience to date has been very encouraging and exciting in that those patients who had evidence of facilitated estrogen uptake into their tumor sites have been the ones that responded to hormone therapy. But we need to have more experience before we can come out and say that everybody should be doing this.

DR. LOVE: Probably the thing that I'm most interested in is clinical decision-making. It's just fascinating to sit and talk to people and how they - I mean, because there's no right answer, really. The point that you brought up that I really hadn't thought about was the kinds of patients that you're seeing and being that you're in a tertiary care setting. When you said that, the first thing I thought about was Nancy Davidson. She's at the same kind of place.

DR. LIVINGSTON: Right. But I think that Nancy's practice and my practice are probably very different, because she's known to be a person with a strong interest in, and I would say even bias toward, hormone manipulation. And vice versa with me. I'm known to have a strong interest in chemotherapy. Does that mean she won't use chemotherapy? Of course not. And I use hormone manipulation all the time. But somebody coming to us for care, especially somebody coming to us for a potential research study, is likely to be selected on the basis of what their doctor knows about us or what they've found out about us.

Home · Search