DR. LOVE: Dr Fox commented in his interview that he believed community-based oncologists tend to first use chemotherapy as opposed to endocrine treatment in women with metastatic disease. And you heard Dr Madej's thoughts on that. But I met with another oncologist in a tertiary setting, Dr Linda Vahdat, and her approach to this patient also differed in many ways from that of Dr Fox.

DR VAHDAT: Basically, even today, there are two major routes you go down. One is that you try to palliate her, which, basically, I look at it as trying to keep them feeling as good as possible for as long as possible. So, I would certainly use effective chemotherapy, which is sort of easy-ish on the side effects, or even think about hormonal blockade in this woman. Or, the other approach for a newly-diagnosed patient for breast cancer could still be a more aggressive route, one that includes aggressive induction chemotherapy, then followed by higher doses of chemotherapy with stem cell support. So, I mean, it all depends on - since we don't know if there's any difference between the two - is there any advantage to the higher doses on a clinical trial? I think you could go down either way. It all depends on the approach that the patient wants to take. So, let's go down the pathway looking at non-transplant. Looking at the non-transplant option, certainly, depending on the number of nodules, how big they are, you could certainly think about trying her on hormones, combined hormones, or what you could think about doing is, you could think about starting her on chemotherapy. And, certainly, if I were going to think about starting her on chemotherapy, I'd probably think about using capecitabine as my first choice.

DR. LOVE: Now, again, this lady's ER-positive, asymptomatic. Another issue comes up about diagnosis. If she had what appeared to be typical metastases, would you be willing to accept that, or would you want tissue from the lungs?

DR VAHDAT: No. I would absolutely get tissue to confirm that diagnosis.

DR. LOVE: And generally speaking, how would you do that?

DR VAHDAT: Well, usually my first choice is a CT-guided lung biopsy. And if they're too small, then usually what I'll end up doing is a VAT, video-assisted thoracoscopy, in order to get the diagnosis. But I would not give her a diagnosis of Stage IV disease no matter how typical it looked, unless I exhausted every possibility to get tissue.

DR. LOVE: One thing that you brought up was hormone therapy. If that were the route you were going to take in this premenopausal, ER-positive patient, generally speaking, what would it be?

DR VAHDAT: Well that's also a tough question. I think you have to think about using an aromatase inhibitor. But, if you think about it, probably an aromatase inhibitor probably isn't enough for her, and she probably needs Zoladex along with that. So, I would either use combined hormonal blockade or tamoxifen.

DR. LOVE: And you mentioned the possibility of giving this woman chemotherapy, and you mentioned high-dose therapy. What would be specifically the regimen you'd consider and what would you tell her in terms of what the risks and benefits would be?

DR VAHDAT: Well, certainly with regard to the existing data, we have two randomized trials as first-line therapy. And, as you know, that's the Philadelphia trial. And the MA-16 out of the Canadian trial. And I would tell her that it appears that roughly nine months of maintenance chemotherapy is equivalent to a single high-dose cycle of chemotherapy with stem cell support. So, in terms of deciding what she would prefer to do, in terms of coming back and forth for chemotherapy, issues regarding quality of life because certainly, in the short term, quality of life is worse with the higher doses of chemotherapy than with maintenance therapy. But we have a Phase II trial of tandem high-dose chemotherapy with stem cell support, then followed with various sort of minimal residual disease strategies, immunotherapy. And then we've gone into a few other places for other modalities. I would certainly tell her that we don't know which is better and that we certainly won't have an idea, because we have a couple of more metastatic trials that will mature probably within the next two to three years. So, I always -when I'm talking to patients about higher doses of therapy - tell them, "You know, they don't know which is better. There's always a possibility that you will get a significant disease-free interval from the higher doses of chemotherapy." But, as many patients that I have, that have been disease - as far as we know, without any progression for six or seven years, I have people who relapse five or six months later. So, basically, again, it comes down to what kind of risks they want to take. Because we know that we can do transplants safely, and usually within a month or two after they finish their therapy, they're back up to where they were before they had the transplant. So, that's sort of how I talk to them about transplant. And I find that the people who really pursue this are usually people who are young, 40 and less. They tend to be people who have had Stage IV breast cancer as their initial diagnosis. They're minimally pre-treated, and they have limited disease, such as maybe bone-only disease or supraclavicular lymph nodes. So, those are the types who I find are typically pursuing the more aggressive options.

DR. LOVE: When you contrasted that, it sounded to me like you were thinking that we don't really have any evidence that there's greater efficacy, but maybe it might be easier to get this over with quickly.

DR VAHDAT: Exactly right. I think a lot of people are looking for that return to normalcy, in terms of not having to come to the doctor's office every week or every three weeks for chemotherapy, to being consistently on therapy. I think they're looking to get away from that. As you and I well know, if someone has advanced disease, there's really no way that they can get away with that. Certainly, you could take a treatment break of about two to three months, but then they're going to be right back where they were before. It's the whole issue of continuous intermittent chemotherapy for advanced breast cancer.

DR. LOVE: If the patient were to say to you, "You've seen a lot of people treated with high-dose therapy, one treatment like this, and you've seen a lot of people get nine months of treatment. Overall, sort of which one seems to be more compatible with a normal quality of life," how would you answer?

DR VAHDAT: Well, tough question. I would say that for most people - well, see, don't forget, I see a very segued population, because they usually come to talk to me about this. They've already been thinking about it. I would say that most people who are young, who have small children, will pretty much pursue the more aggressive option on the chance that they will have less disruption to their lives for a longer period of time. They know it's no guarantee. But that's the profile of somebody that I see, who would pursue the high-dose therapy for advanced disease.

DR. LOVE: I would have guessed that people would be more thinking about the possibility, although we don't really have any data to support it, that by taking high-dose therapy they might be cured or have a much greater benefit.

DR VAHDAT: Well, the thing is, when we used to talk to people about high-dose chemotherapy with stem cell support, we used to tell them that, you know, that there certainly is data that patients are disease free for eight or nine years. And, at least, I think that those people are cured. But I think we've sort of shied away from saying that "cure" word because of the Canadian and the Philadelphia data, where it really looks like it's equivalent. You know, you never know. It always seems to come down to about 20 percent disease free long term. And are they cured or not? That's the question. If their disease ever comes back, you might think that it's 10 or 20 years later, you might actually say they have been cured.

DR. LOVE: Well, I think whether they're cured or have very prolonged disease-free interval, to me, I think more the question is: Would they achieve the same thing with conventional chemotherapy?

DR VAHDAT: That's correct. And, looking at the tandem transplants, we don't know the answer to that question. But there is an Irish trial - well, actually, it's a European Trial, the IPTIS trial, which was just closed, which is addressing that question. And then there's a German trial, which is also addressing this question, tandem versus standard therapy. And if I had to guess, I would think that probably tandem is going to be better than single. And if single is equivalent to maintenance chemotherapy, I think that maybe tandem might be the way to go. But I don't think it's the only thing. I mean, I think it needs to be part of an overall treatment strategy, not just - the chemo's going to maximally reduce you, then you need to come in with some other minimal residual disease strategies. Whether it's anti-angiogenesis agents, different antibodies. It's not going to be just one thing. And I think that's becoming more apparent.

DR. LOVE: Well, when I first presented this case to you, you raised the issue of are you going to approach it from a palliative point of view or some other point of view. It sounds to me like somewhere inside of you, you feel that by using a more aggressive approach, perhaps you can achieve something with chemotherapy that you can't with hormonal therapy in terms of long-term outcome.

DR VAHDAT: I think that just by palliating people, you're just putting your finger in the dam. At some point in time they are going to have uncontrolled disease, which they may have anyway, if you do the more aggressive therapy. But you know for sure when you're palliating somebody, all you're really doing is buying time. And depending on the situation, that may be what everybody's goal is.

DR. LOVE: That's interesting. You also brought up the issue of Xeloda in this situation, in this kind of patient. Why would you use Xeloda? You're talking about as monotherapy?

DR VAHDAT: Yes, as monotherapy.

DR. LOVE: Why would you use that as opposed to, say, hormone therapy?

DR VAHDAT: I think that if, by looking at the scans, I felt that she needed a response relatively quickly - quickly being that, as we know, hormones can take up to a couple of months to start to exert an effect. I think that based on, if she had mediastinal lymph nodes, larger nodules, I think that I probably would be concerned that she would become symptomatic from her disease before the hormones really had a chance to exert any effect. So, that would be when I would consider using chemotherapy first-line. And that's not to way that once I maximally site reduce after whatever standard chemotherapy I'm using, that I wouldn't go to hormones to sort of maintain her.

DR. LOVE: But you're saying that, if that was your thinking, one of the thoughts you would have if you needed a quick response, would be single-agent capecitabine?

DR VAHDAT: Yes. That would be, again, depending on what volume of metastases she has. I don't think that I would use capecitabine if I needed a response tomorrow. From my experience with capecitabine, that it takes two or three cycles in order to see an effect. If you look at the data, their maximal response is at about four cycles. So, I think that if someone was fairly asymptomatic, but I didn't feel comfortable about putting them on hormones, I would definitely put them on capecitabine, because it's an oral medication. It's usually well tolerated. Their outward appearance is rarely changed, at least in the beginning. So, I think it's a good option.

DR. LOVE: And what would you use if you did need a response tomorrow?

DR VAHDAT: A taxane.

DR. LOVE: Single agent?

DR VAHDAT: Yes. I'm a single-agent person. I like single agents.

DR. LOVE: You talked about the issue of using in a patient like this a combination of an LH-RH agonist and an aromatase inhibitor. Can you talk a little bit about how aromatase inhibitors have sort infiltrated into your practice, both in terms of metastatic disease, but also whether there are any situations in the adjuvant setting, where you substituted an aromatase inhibitor for tamoxifen?

DR VAHDAT: Well, to start with your last question first, I think it's important to maintain as close to standard therapy as possible when you're approaching a patient in the adjuvant setting. Because there's no circumstance where you really want to compromise their chance of being cured of their disease. But we certainly know that many patients - well, not many, but there are going to be some patients who are intolerant of tamoxifen or tamoxifen is contraindicated. There could be prior history of thromboembolic disease. So, there are going to be some patients that cannot take tamoxifen. And those are the patients that I will give an aromatase inhibitor to, even though there is no long-term adjuvant data for either one of them - actually, for any of them right now. As you know, those trials are in the process of being done or, I think, one of them might be completed, but we don't have data yet. But, certainly, when you look at the data in metastatic disease - and you can certainly consider extrapolating to the adjuvant setting, at least to say that you wouldn't expect it to be any worse. But that's where I use them in the adjuvant setting. But, now, to talk about how it's infiltrated into my practice for metastatic disease, I think the aromatase inhibitors are, in general, wonderful drugs, very well tolerated.

DR. LOVE: What are some of the other things in your practice over the last two or three years, that have changed in terms of your day-to-day practice? You mentioned the aromatase inhibitors changing your algorithm in terms of metastatic disease. When you look both at metastatic disease in the adjuvant setting right now, compared to, say, two or three years ago, anything else that's changed?

DR VAHDAT: Two to three years. I guess it's about the time the bisphosphonates really became widely used. Maybe about three years ago - could even be four years ago - and for metastatic disease. So, pretty much, everybody gets a bisphosphonate. I'm intrigued by the adjuvant data, and I have many patients who get Clodronate from Canada. And there's going to be a big Intergroup trial look at Zoledronate, which is going to be very exciting to participate in. In terms of other things, I think another sort of unanswered question - and we're sort of all over the place about it - is, you know, what to do with Herceptin, how to measure it, how to give it.

DR. LOVE: What are you doing right now in terms of that?

DR VAHDAT: Well, right now, I'm giving it continuously, and I'm giving it once a week. But I'm hoping that we're going to see some good data on a, like, a once-every-three-weeks schedule. Because I think it really ties the patients down, the once a week schedule. But then, if you're looking to palliate people, you want to have them live as normal life as possible, and not bring them in every week or have a home-care company come to their house every week to give them Herceptin.

DR. LOVE: Are you're using a single agent combined with chemotherapy, both?

DR VAHDAT: Well, I'm doing both actually. If someone has low volume disease, like a supraclavicular lymph node, I will probably try them on Herceptin alone to begin with, and see what happens. Because, as you know, you will get some people to respond to Herceptin monotherapy. And if they respond, have stable disease or respond, I keep them on Herceptin monotherapy until they progress, and then I'll add something in. And then, of course, that adding in will depend on where the disease is. And for a patient who I need a response tomorrow, I won't use Herceptin by itself. I'll combine it with chemotherapy, usually a taxane.

DR. LOVE: And which taxane?

DR VAHDAT: It varies. I'd say 50 percent Taxol, 50 percent Taxotere.

DR. LOVE: And is that sort of emblematic of your practice in general in terms of metastatic disease and taxanes?

DR VAHDAT: I tend to give a little bit more Taxol, because I've had a lot of problems with the steroids with the Taxotere. This giving them the steroids, for three days every week has been very rough on a lot of patients.

DR. LOVE: And you said that in some instances you do use Taxotere with Herceptin?

DR VAHDAT: Yes, I do. And, also, I pretty much use every chemotherapy with Herceptin, even though there's no randomized data, of course, for anything other than Adria and Taxol.

DR. LOVE: Does that mean that there are situations where patients who are receiving Herceptin either by itself or with chemotherapy, that when they progress you continue the Herceptin?

DR VAHDAT: Yes. That has been what I've been doing.

DR. LOVE: How many times will you do that before you stop? Or do you keep the patient on Herceptin indefinitely? Or how do you approach it?

DR VAHDAT: Most patients, I do. And that's basically because of the data that suggests that there might be a survival advantage. But, I can't say that I know it's the right thing to do, but that's what I've been doing.

DR. LOVE: What about some of the large Phase III cooperative studies that have been completed but haven't yet reported data? We talked before about the ATAC trial. Any others that are completed and probably going to provide some results in the next couple of years that you're going to be curious to see?

DR VAHDAT: Well, I think that there are a lot of trials, actually. One of the major issues in the adjuvant treatment of breast cancer is whether you should add a taxane or not. And I think we're going to continue to get follow-up data on the CLGB-9344, which is AC followed by a placebo or a taxane, and also NSABP B-28. You know, both of these trials have follow-up less than five years. I think we'll probably see an update within one to two years to sort of see - at least help us figure out do taxanes add anything to further reduce the risk of recurrence or death from breast cancer in the adjuvant setting. So, I think that's going to be an important trial.

DR. LOVE: Let me ask you: What are you doing right now in a non-protocol setting in terms of use of adjuvant taxanes?

DR VAHDAT: I give them. I'm basically of the opinion that I think that ultimately the taxane data will prove positive. So, I usually recommend a taxane. Now, there are certain exceptions to this rule. In terms of young women you're always concerned about, or at least they're the most concerned about fertility, especially if they've never had any children. And those types of patients would probably tend to do more CMF or even an AC.

DR. LOVE: So, is it your thought that maybe the taxanes are going to have more of an effect on fertility? Because I'm not sure I've seen data on that.

DR VAHDAT: I think there's a higher rate of amenorrhea, but that's just slightly higher than standard doses of Taxol. I think that came out of the ATC trial.

DR. LOVE: That's interesting. So, first of all, which taxane are you using in an adjuvant setting?

DR VAHDAT: I use Taxol.

DR. LOVE: And so you use ACT pretty much like the protocols?

DR VAHDAT: But, I've been very lucky that I've been pretty much able to put everyone on the Intergroup trial, which does have a taxane. So, that makes it easy, sort of a chickening out. So, I put pretty much all the node-positives on that trial. The other trial, which I guess we're not going to hear for several years, is the AC versus Adria-Taxotere trial, which is, again, another big Intergroup trial. So, that's going to be interesting to see if that adds anything in the node-negative setting. And then there's another SWOG trial, which I don't recall the number, but basically it's looking at q two week versus q three week chemo, sort of looking at the dose-dense chemotherapy concept. So, if there's an advantage to shortening the interval, that may actually shift how we treat patients. And then, of course, there are a whole bunch of high-dose trials, which will probably be reported in the next two to three years.

DR. LOVE: Are you using taxanes in any node-negative patients?

DR VAHDAT: No. Only on trial.

DR. LOVE: It's interesting. I guess I picked up from you, I was kind of interested, and maybe it's because of the way you're working and the culture of your group, but I was very curious about your thoughts about high-dose therapy. Are you recommending high-dose therapy to a lot of patients with metastatic disease off protocol?

DR VAHDAT: No. We only do it on protocol.

DR. LOVE: That's interesting.

DR VAHDAT: Well, we don't really know what its role is, if any. And I think that we have to be in a situation where we learn something from it. Now, unfortunately, we were part of the IPTIS trial, which is the international trial, and that closed about a month ago, which was sort of sad, because that was a very good trial. But, there's not the same volume of interest that there was in transplant, say, three or four years ago. So, you have to recognize that and just sort of go with the flow.

DR. LOVE: Do you think that there are a lot of patients right now receiving transplant, even in the adjuvant or metastatic setting, right now in the community off protocol?

DR VAHDAT: No, I do not. I don't think so at all. I think one of the things that's happened over the past few years, that instead of every hospital having a stem-cell transplant program, that basically it's now come back to the big centers in terms of the expertise. You know, sending people back to the centers that do it, which is great, because they're expensive programs. You need to have a lot of infrastructure for it. And that's the only good thing that's happened out of all of this. It's sort of a shame that we can't do the trials that our colleagues in Europe can.

You know, you had asked me about the adjuvants, too. There was a great adjuvant, Intergroup adjuvant trial that closed in February. It basically took patients who had four or more positive lymph nodes and randomized them to q two week Adria for three, Taxol for three, and Cytoxan for three, at higher standard doses, versus AC with the Adria at 82 milligrams per meter squared followed by transplant. So, that was a really good trial that we used to put a lot of people on. But now what we're doing is when people come to talk to us who are high-risk adjuvant, ten or more positive nodes or Stage III's or the inflammatories, we put them on our institutional trial, which is basically "Stamp"-5 followed by immunotherapy.

DR. LOVE: Now, is that randomized?

DR VAHDAT: The immunotherapy part is randomized but not the transplant. It's a Phase II.

DR. LOVE: This concludes our program. For more information on the subjects discussed, please consult the enclosed web guide and BreastCancerUpdate.com which has hundreds of web links to articles and protocols mentioned by the speakers. Special thanks to our speakers and thank you for listening…this is Dr Neil Love for Breast Cancer Update

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