CATHY CONLEY: Hi, I'm Cathy Conley, here at the San Antonio Breast Cancer Symposium, where an important topic has been improving the safety and efficacy of current breast cancer therapies. I had a chance to sit down with some of the experts to discuss issues surrounding a popular class of drugs called anthracyclines.
JOYCE O'SHAUGHNESSY, MD: It's pretty clear now that anthracycline-based therapy, called adjuvant chemotherapy, after the primary tumor has been removed, is where you're going to get your greatest survival advantages, to cure the most number of women. So that's why we use the anthracycline chemotherapy regimens.
TERRY P. MAMOUNAS, MD: There's very convincing evidence that adjuvant chemotherapy in general will improve survival, and certainly that's including evidence that anthracycline-containing therapy is actually more effective than non-anthracycline-containing therapy.
CATHY CONLEY: The benefits of anthracyclines include longer survival and longer time to remission. But what about the differences between the anthracyclines epirubicin and doxorubicin?
JOYCE O'SHAUGHNESSY, MD: They are both used for women where the primary breast cancer has been removed, and they have just been incorporated into different regimens. One is called CAF, and the other one is called CEF. You can see that the only difference there is whether you're using the adriamycin or the epirubicin, adriamycin, or Ellence -- the other name for epirubicin. But they are both used -- you don't use them together. You use them as part of combination chemotherapy, because we do know, also, from clinical trials that combinations of chemotherapy cure more women than just using one agent by itself.
TERRY P. MAMOUNAS, MD: Although those two anthracyclines are very similar in structure, minor differences in structure result in certain differences in the pharmacology in terms of uptake of the drug and metabolism of the drug. As a result of that, there are some differences in clinical endpoints. Certainly, there are differences in toxicity, particularly cardiotoxicity. So if you compare the two anthracyclines milligram per milligram, epirubicin is less cardiotoxic than doxorubicin.
As a result, epirubicin has been able to be intensified in higher doses of anthracycline, and several studies have shown that by increasing the dose of epirubicin, one can get actually an increase in benefit as compared to the other anthracyclines, adriamycin or doxorubicin, which actually we haven't been able to show and differences by intensifying its dose.
KATHLEEN PRITCHARD, MD: I think the biggest window of difference is for the cardiac effects, where you can give almost twice as much, milligram per milligram, epirubicin as you can adriamycin before seeing the same kind of cardiac problems.
CATHY CONLEY: At this meeting, a lot of attention has been placed on hormonal therapy and targeted therapy. But how are these advances impacting the use of anthracyclines in the adjuvant setting?
TERRY P. MAMOUNAS, MD: Advances in hormonal therapy don't necessarily make much difference in terms of the use or nonuse of anthracycline-containing regimens or other adjuvant chemotherapy.
There are some examples, though, of targeted therapy -- for example, Herceptin comes to mind -- where it's very difficult to give Herceptin with an anthracycline-containing regimen because of increased cardiotoxicity. So from that standpoint, as we advance the use of Herceptin in the adjuvant setting, we'll have to make some decisions in terms of how to use it relative to the anthracycline-containing regimens.
The approach that we have taken, among all the cooperative groups, is to give anthracycline-containing regimens first, and follow this by Herceptin. So we don't give them in conjunction, but we give them sequentially.
HOPE RUGO, MD: There's a lot of interest now in looking at, perhaps, epirubicin, where you use less -- you don't reach that heart-toxic dose as easily, so maybe if you could use epirubicin in these Herceptin-containing treatment programs.
CATHY CONLEY: Anthracyclines can be used in various combinations, and the latest research is showing us how to best use these combinations.
KATHLEEN PRITCHARD, MD: There are a number of planned trials for anthracycline-containing regimens in the future. One that we're involved with is comparing the CEF regimen we developed in Canada to an AC followed by Taxol regimen that's been a standard in the United States, with a third, experimental arm that has a very intensive epirubicin-cyclophosphamide component, then followed by a taxane. That's one that we're running in Canada and the United States now.
HOPE RUGO, MD: There's another area where adjuvant treatment is changing, and that is in combining the anthracyclines with another very active group of chemotherapy drugs called taxanes, and there has been a lot of interesting data now presented that the response rates in advanced breast cancer are much higher when you combine these drugs together. But there are more side effects. So in advanced breast cancer, we want to see that people are going to live longer before we use that.
But in early stage breast cancer, of course, we're willing to take a little more side effects in the short term for more cures. So there's a lot of interest now in combining anthracyclines like epirubicin with taxanes to try and improve long-term survival without recurrence from breast cancer.
JOYCE O'SHAUGHNESSY, MD: It's pretty clear now that anthracycline-based therapy, called adjuvant chemotherapy, after the primary tumor has been removed, is where you're going to get your greatest survival advantages, to cure the most number of women. So that's why we use the anthracycline chemotherapy regimens.
TERRY P. MAMOUNAS, MD: There's very convincing evidence that adjuvant chemotherapy in general will improve survival, and certainly that's including evidence that anthracycline-containing therapy is actually more effective than non-anthracycline-containing therapy.
CATHY CONLEY: The benefits of anthracyclines include longer survival and longer time to remission. But what about the differences between the anthracyclines epirubicin and doxorubicin?
JOYCE O'SHAUGHNESSY, MD: They are both used for women where the primary breast cancer has been removed, and they have just been incorporated into different regimens. One is called CAF, and the other one is called CEF. You can see that the only difference there is whether you're using the adriamycin or the epirubicin, adriamycin, or Ellence -- the other name for epirubicin. But they are both used -- you don't use them together. You use them as part of combination chemotherapy, because we do know, also, from clinical trials that combinations of chemotherapy cure more women than just using one agent by itself.
TERRY P. MAMOUNAS, MD: Although those two anthracyclines are very similar in structure, minor differences in structure result in certain differences in the pharmacology in terms of uptake of the drug and metabolism of the drug. As a result of that, there are some differences in clinical endpoints. Certainly, there are differences in toxicity, particularly cardiotoxicity. So if you compare the two anthracyclines milligram per milligram, epirubicin is less cardiotoxic than doxorubicin.
As a result, epirubicin has been able to be intensified in higher doses of anthracycline, and several studies have shown that by increasing the dose of epirubicin, one can get actually an increase in benefit as compared to the other anthracyclines, adriamycin or doxorubicin, which actually we haven't been able to show and differences by intensifying its dose.
KATHLEEN PRITCHARD, MD: I think the biggest window of difference is for the cardiac effects, where you can give almost twice as much, milligram per milligram, epirubicin as you can adriamycin before seeing the same kind of cardiac problems.
CATHY CONLEY: At this meeting, a lot of attention has been placed on hormonal therapy and targeted therapy. But how are these advances impacting the use of anthracyclines in the adjuvant setting?
TERRY P. MAMOUNAS, MD: Advances in hormonal therapy don't necessarily make much difference in terms of the use or nonuse of anthracycline-containing regimens or other adjuvant chemotherapy.
There are some examples, though, of targeted therapy -- for example, Herceptin comes to mind -- where it's very difficult to give Herceptin with an anthracycline-containing regimen because of increased cardiotoxicity. So from that standpoint, as we advance the use of Herceptin in the adjuvant setting, we'll have to make some decisions in terms of how to use it relative to the anthracycline-containing regimens.
The approach that we have taken, among all the cooperative groups, is to give anthracycline-containing regimens first, and follow this by Herceptin. So we don't give them in conjunction, but we give them sequentially.
HOPE RUGO, MD: There's a lot of interest now in looking at, perhaps, epirubicin, where you use less -- you don't reach that heart-toxic dose as easily, so maybe if you could use epirubicin in these Herceptin-containing treatment programs.
CATHY CONLEY: Anthracyclines can be used in various combinations, and the latest research is showing us how to best use these combinations.
KATHLEEN PRITCHARD, MD: There are a number of planned trials for anthracycline-containing regimens in the future. One that we're involved with is comparing the CEF regimen we developed in Canada to an AC followed by Taxol regimen that's been a standard in the United States, with a third, experimental arm that has a very intensive epirubicin-cyclophosphamide component, then followed by a taxane. That's one that we're running in Canada and the United States now.
HOPE RUGO, MD: There's another area where adjuvant treatment is changing, and that is in combining the anthracyclines with another very active group of chemotherapy drugs called taxanes, and there has been a lot of interesting data now presented that the response rates in advanced breast cancer are much higher when you combine these drugs together. But there are more side effects. So in advanced breast cancer, we want to see that people are going to live longer before we use that.
But in early stage breast cancer, of course, we're willing to take a little more side effects in the short term for more cures. So there's a lot of interest now in combining anthracyclines like epirubicin with taxanes to try and improve long-term survival without recurrence from breast cancer.