Hair loss Treatment Center

PARTICIPANTS Kathleen I. Pritchard, MD Regional Cancer Center, Toronto, Canada Hyman B. Muss, MD Associate Director for Cancer Research, Vermont Cancer Center

Dr. Pritchard, what is adjuvant therapy, and why is it necessary?

KATHLEEN PRITCHARD, MD: Adjuvant therapy really means therapy that's given in addition to the primary therapy. For breast cancer, after diagnosis, the primary therapy is to remove the breast cancer, perhaps remove axillary lymph nodes and radiate the breast. Adjuvant therapy is hormonal therapy or chemotherapy that's given in addition to that in order to reduce the risk of recurrence of the breast cancer.

CATHY CONLEY: Doctor, it's now widely accepted that adjuvant chemotherapy containing an anthracycline is better than the historical treatment known as CMF. Why is that?

HYMAN B. MUSS, MD: There's a very wonderful thing that we've all participated in clinical trials called the Worldwide Overview, and they have data on about 190,000 women from all over the world, many American women, Canadian women who have been put in randomized trials comparing one drug with another by a coin flip, and in their trials, they've looked at the anthracyclines versus more traditional therapies like CMF, which are among the original adjuvant therapies that were so successful in improving survival. In the overview, the use of anthracyclines has further added to the benefits of CMF by about 10 to 15%. In those overviews, which are pretty convincing overall, I think it's pushed many physicians to consider anthracycline use. But again, in older women -- for instance, in their 70s -- and people with heart disease and others, their use is of great concern.

CATHY CONLEY: Doctor, what are the side effects of anthracyclines, and is there a difference between the two agents?

HYMAN B. MUSS, MD: Well, anthracyclines' major side effect is lowering blood counts. Both epirubicin and doxorubicin can be very damaging to the marrow. It's a transient effect in most patients, lower counts. When you have low blood counts, especially low white cell counts, you're at higher risk of infection, and that is the most dangerous side effect of chemotherapy.

Other side effects, like nausea and vomiting, we're actually very good with these days. Thinks like mouth sores, which can be very rough to have, are probably similar among the agents, and then, as we talked about with cardiac toxicity, the heart damage, probably in the doses they're given, it's probably not a major problem for either anthracycline if a patient is closely monitored. When you get to high doses, there might be some advantage for epirubicin.

CATHY CONLEY: Dr. Pritchard, is there anything you'd like to add?

KATHLEEN PRITCHARD, MD: Either adriamycin, the older anthracycline, or epirubicin, the newer anthracycline, both have cardiac effects, but you can give almost twice as much epirubicin as adriamycin before seeing the same cardiac effects, and the two drugs appear to be almost equivalent or barely different in terms of their antitumor effect. So you have a window where you can give more epirubicin with more effect on the tumor and less risk of cardiac effect.

CATHY CONLEY: We hear the term "five-year survival rate." What does this mean?

KATHLEEN PRITCHARD, MD: In many cancers, a patient who does not have a recurrence after five years is considered cured. In breast cancer, that's probably not the case, but we do look at outcomes at five years, ten years and 15 years as a mark of how a patient is progressing through their life after they have a diagnosis of breast cancer.

CATHY CONLEY: Dr. Muss, we hear a lot about dose-limiting toxicity or cumulative toxicity. What does this mean?

HYMAN B. MUSS, MD: In general oncology in adjuvant therapy, we believe achieving a certain threshold dose of treatment is important. In other words, if a woman goes below a certain dose, we believe that therapy is definitely not going to be as effective. So a dose-limiting toxicity would be a side effect that prevents you from giving a certain dose of medication. Now, if that dose was lower than the threshold, then it would be very important, because you might not be giving the patient adequate treatment, and you would have to consider something else.

Cumulative dose means taking a drug like an anthracycline and measuring actually the amount of drug that's given, like we take pills in milligrams. So we count all the milligrams up that you've gotten in your treatment, and we divide it by your body surface area, which we get by your height and weight, and those data allow us to get a certain dose level where we know if we exceed it we're likely to cause heart damage.

CATHY CONLEY: Dr. Pritchard, you spoke at this breast cancer symposium about the benefits, the survival benefits of anthracycline-based therapy. Can you give us some main points?

KATHLEEN PRITCHARD, MD: I think the shorter anthracycline-containing regimens such as AC are not better than CMF. They're as good as CMF, but they don't provide significantly more disease-free or significantly better overall survival. The regimen that we developed in the Canadian Trials Group, CEF, contains epirubicin. We gave it twice every month, the epirubicin twice every month in as a high a dose as we could, staying within the safe cumulative doses, and we have shown in a single trial that that regimen is better both for disease-free and overall survival than CMF in our group of patients who are premenopausal and have positive lymph nodes.

CATHY CONLEY: Have there been any head-to-head trials comparing doxorubicin to epirubicin?

KATHLEEN PRITCHARD, MD: There have been many head-to-head trials comparing doxorubicin and epirubicin in combinations and as single agents in metastatic disease, and in that setting it looks as though, milligram for milligram, epirubicin and doxorubicin are very similar in their effect against tumors. The trick in the adjuvant setting is that you can get more of the epirubicin in over a shorter period of time and a total larger dose without doing the cardiac damage that you would see with a similar dose of adriamycin.

CATHY CONLEY: And finally, Dr. Pritchard, what advice do you have for our viewers?

KATHLEEN PRITCHARD, MD: I'd advise them to read all they can and learn all they can on the internet, in books, in magazines, and to talk to their physicians about what they read, and understand whether it applies to them.

CATHY CONLEY: Dr. Pritchard, thanks so much for joining us.

KATHLEEN PRITCHARD, MD: Thank you very much.

CATHY CONLEY: Dr. Hyman Muss, thank you for joining us.