CAN-NCIC-MA21 dose-dense chemotherapy adjuvant trial

We are conducting a trial that many Americans are participating in, comparing CEF versus dose-dense EC plus G-CSF followed by paclitaxel versus AC followed by paclitaxel, which was one of the comparative arms of CALGB-9741. This may give us a lot of cross-reference points to compare all of these regimens.

In Canada we continue to use CEF as one of our standard arms, but we chose EC in this trial instead because it can be given in a 12-week schedule and we wanted to sequence paclitaxel with what we were already doing. In addition, our previous trial had already shown the EC and CEF regimens to be equivalent. We added erythropoietin to the EC arm to prevent the anemia and sequenced the paclitaxel after it, which resulted in a six-month regimen.

Management of the patient with metastatic breast cancer

I manage patients with metastatic disease palliatively. I don’t mean palliative as in end-of-life, because we have more effective treatments, and I believe these patients are living longer. I try to treat them as gently as possible for as long as I can, and I use hormones, hormones and more hormones.

I also use bisphosphonates in any patient with bone disease. I think these agents have made a huge difference in quality of life for these patients. I no longer see patients with multiple fractures and terrible bone problems. Nor do I see hypercalcemia as often as I once did. The bisphosphonates have been a great boon for patients in the metastatic setting.

Chemotherapy in the metastatic setting

We seem to be giving more and more lines of chemotherapy to patients with metastatic disease. We see good responses to first-line and second-line therapy, so we try third- and fourth-line treatments. Although we all seem to keep giving it, I wonder whether it’s worth it. It would be nice to have more approaches with less toxicity.

I don’t use the same doses of agents in the metastatic setting that I use in the adjuvant setting, and I don’t use colony-stimulating factors as much in this setting, because I’m treating for palliation. I reduce doses by a quarter or a third and simply treat patients more gently. For example, with capecitabine, the doselimiting toxicity is usually hand-foot syndrome. But this agent works great if you start out at 75 percent of the full dose. My theory is that if I hospitalize patients as a result of toxicities, it may be two weeks or a month out of their life, and who knows how much more time they have.

Capecitabine/docetaxel in the metastatic and adjuvant settings

When Dr Joyce O’Shaughnessy presented the positive data from the capecitabine/docetaxel trial in the metastatic setting, I was surprised by the results. Many of us thought there would be no significant difference. We had compared doxorubicin with and without vinorelbine and didn’t see a significant difference, so we expected to see the same results with this study. The data is exciting and I think it warrants examination in the adjuvant setting. If we can treat these patients for three to six months and have them be well for five or ten years, that’s worth studying.

Management of patients with ER-negative, HER2-negative metastatic breast cancer

In the metastatic setting, I generally treat ER-negative patients with an anthracycline-containing regimen first and a taxane or taxane-containing regimen second. I use capecitabine in patients who are relatively asymptomatic and want something milder or prefer oral therapy. Otherwise, I tend to use this agent in the third-line setting. Many of our patients have failed adjuvant anthracyclines, so it’s usually a choice of either a taxane-containing regimen or something a bit milder. We use a lot of capecitabine and vinorelbine, but we don’t know how their response rates compare to anthracyclines or taxanes. My guess is that it doesn’t make a lot of difference.

Progress in the management of breast cancer

We’ve made significant progress overall in terms of breast cancer screening and adjuvant therapy. We’re seeing smaller cancers and earlier cancers. We are also seeing fewer cancers that turn into metastatic disease, or if they do, it takes longer. I believe that a large part of this progress in adjuvant therapy can be attributed to the use of hormonal therapy, primarily tamoxifen, as opposed to chemotherapy, although I think we’ve made progress in both areas.

We’ve also certainly seen improvement in the quality of life of patients with metastatic disease, and some of that is from unexpected places like the bisphosphonates. We have seen very radical operations disappear. As much progress as we have seen in the management of breast cancer, we could still stand to see more. While I think we’ll be using some of the same modalities, I believe that we are headed towards gene arrays and targeted therapy.

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