Phase 3 clinical trial evaluating the safety and efficacy of adding docetaxel to doxorubicin and cyclophosphamide chemotherapy in node positive breast cancer patients

In this phase 3 clinical trial, two types of adjuvant (a treatment given in addition to a main treatment) chemotherapy regimens were compared in women with node positive breast cancer after surgery to remove the cancer. These were the combination of docetaxel (Taxotere), doxorubicin and cyclophosphamide (TDC) or the combination of fluorouracil, doxorubicin and clyclophosphamide (FDC). 

Node positive breast cancer means that the cancer has spread from the breast to the surrounding lymph nodes. These usually include the lymph nodes under the arm or those above or under the collarbone. Patients with node positive breast cancer are usually treated with surgery to remove the cancer from the breast along with the affected lymph nodes (the main treatment), followed by chemotherapy to remove whatever cancer cells are still in the body. This is called adjuvant chemotherapy and usually lowers the risk that the cancer will return (recurrence). Standard chemotherapy for patients with this stage of breast cancer usually involves a chemotherapy regimen based on FDC. Recent studies have showed that the addition of docetaxel to such regimens may lower the risk of breast cancer recurrence and bring survival benefits to these patients. This study aimed to evaluate the safety and efficacy of adding docetaxel to doxorubicin and cyclophosphamide therapy (TDC regimen).

In all, 1491 patients from 20 countries, with node-positive confined breast cancer participated in this study. All patients had surgery to remove the cancer from the breast and lymph nodes. They were randomly assigned to adjuvant treatment, either with TDC or with FDC every 3 weeks for six cycles. Parameters measured were disease free survival or DFS (defined as the percentage of patients who were cured of the disease after a certain time from treatment), overall survival or OS (defined as the percentage of patients who have survived for a certain period of time after treatment) and side effects of chemotherapy.

After approximately 10 years of follow up, DFS of patients in the TDC group was 62% compared to 55% in patients treated with FDC. OS was also higher for patients treated with TDC (76%) compared to patients who received FDC (69%). The most severe side effects of chemotherapy were heart problems and they occurred in both patients treated with TDC (17%) and those treated with FDC (15%), probably caused by doxorubicin treatment. 

In this study, treatment with adjuvant TDC resulted in improved survival rates compared to treatment with adjuvant FDC in node-positive breast cancer patients. However, both treatments were associated with important heart complications.

This study was funded by Sanofi, the manufacturer of Taxotere.