Results from a Canadian-led clinical trial suggest that a standard chemotherapy combination regimen for breast cancer is not as effective as chemotherapy regimens more commonly used in Canada in preventing recurrence of breast cancer. The preliminary findings were presented by the lead researchers December 17 at the San Antonio Breast Cancer Symposium.

The trial involved 2,104 women under age 60 in Canada and the U.S. who were diagnosed with lymph node-positive or high-risk, node-negative breast cancer, which accounts for almost 50 percent of breast cancer cases in North America. Following surgery, they were randomly assigned to one of three different 6-month, intravenous treatment regimens: AC/T (doxorubicin and cyclophosphamide followed by paclitaxel administered every 3 weeks), one of the standard of care regimens used in the United States; CEF (cyclophosphamide, epirubicin and fluorouracil), which was developed and used in Canada; or the experimental regimen dose-dense EC/T (epirubicin and cyclophosphamide followed by paclitaxel).

An interim analysis showed that the 3-year, recurrence-free survival rate was 85 percent for patients on AC/T, compared with 90.1 percent for patients on CEF, and 89.5 percent for those on EC/T. Final trial results are not yet available, but half of the patients included in this interim analysis were followed for at least 30 months.

Initial data analysis shows that AC/T is "significantly inferior" to the CEF and EC/T regimens in preventing a recurrence of the disease, commented research co-leader Dr. Margot Burnell, an oncologist from New Brunswick, Canada.

The study was funded in part by the Canadian Cancer Society and coordinated by the National Cancer Institute of Canada Clinical Trials Group, with additional funding by NCI and several pharmaceutical companies.

Although final results from this clinical trial "may change the way many [breast cancer patients] are treated in the future," Dr. Burnell cautioned that use of AC/T will not likely be totally discontinued. "AC/T administered at the standard 3-week intervals may still be the right choice for some patients depending on factors such as their general state of health and how well they tolerate the side effects of different chemotherapy drugs."

"The results are interesting," said Dr. Jo Anne Zujewski of NCI's Cancer Therapy Evaluation Program. "Although there is interest in the CEF and EC/T regimens used in Canada, there was more toxicity, including serious and long-term toxicity. There were a lot of variables in this trial so that it is hard to identify what factor is accounting for the results." She also noted that the U.S. cooperative group, CALGB, reported in their study that administering AC/T every 2 weeks - called "dose dense" - was superior to the 3-week schedule of AC/T used in the Canadian trial.

The study's researchers say it is too early to determine whether CEF is more effective than the experimental EC/T treatment. It is also premature to say whether overall survival, as opposed to recurrence, is better on any one of the three regimens.

By Bill Robinson