Neoadjuvant Docetaxel Increases Response Rate in Large Breast Tumors

ABERDEEN, Scotland—Primary, or neoadjuvant, chemotherapy with docetaxel (Taxotere) substantially increases the response rate in breast cancer patients who have received initial treatment with a chemotherapy combination, results of a phase III Scottish study demonstrate.

Almost half of a group of patients with large or locally advanced breast tumors had a major response to docetaxel after failing to respond to neoadjuvant treatment with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CVAP). Among patients who responded to CVAP, docetaxel increased the overall response rate by 40%.

“Docetaxel should be considered in the management of all patients receiving primary chemotherapy for large and locally advanced breast cancer,” Dr. Oleg Eremin said at the San Antonio Breast Cancer Symposium. “Further studies are needed to define the optimal regimen.”

Neoadjuvant chemotherapy downstages tumors in the breast and axilla and increases the likelihood of breast-conserving surgery, noted Dr. Eremin, an oncologist with the Aberdeen Breast Group at Grampian University Hospital and the National Health Service, Aberdeen, Scotland. “Disease-free survival and overall survival are not compromised with neoadjuvant chemotherapy, and anthracycline regimens are regarded as the gold standard,” Dr. Eremin said.

The investigators enrolled 163 patients who had large breast tumors (greater than 3 cm) or locally advanced breast cancer (T3, T4, and N2) and no history of chemotherapy. All the patients received four 3-week cycles of CVAP, which consisted of cyclophosphamide 1,000 mg/m², doxorubicin 50 mg/m², vincristine 1.5 mg/m², and prednisolone 40 mg for 5 days.

After completion of CVAP, each patient was evaluated for response. Those who achieved a partial or complete response were randomized to receive four more cycles of the combination therapy or four cycles of do-cetaxel 100 mg/m². Patients whose tumors did not respond to CVAP received four cycles of docetaxel.

At the completion of eight cycles, each patient had breast surgery and axillary node dissection.

The 163 patients had a 66% overall response to primary therapy with CVAP, including complete responses in 14% and partial responses in 52%. The 52 responders who were randomized to continue CVAP had no further overall improvement in response (67% after eight cycles). The rate of complete response did increase to 33%.

In contrast, Dr. Eremin said, the 49 CVAP responders randomized to docetaxel had a 94% response rate at the end of four cycles of taxane treatment, including complete responses in 61%. Of the patients who did not respond to primary CVAP, 47% subsequently responded to docetaxel, including complete responses in 10% and partial responses in 37%.

Pathologic Responses

Docetaxel also increased the rate of pathologic response. Patients who received eight courses of CVAP had a 57% pathologic response rate, which increased to 79% in CVAP responders who were randomized to docetaxel. A 42% pathologic response rate was seen in patients who did not respond to CVAP and were then treated with docetaxel.

Psychological status and quality of life were assessed by means of several standardized testing instruments. Dr. Eremin noted that scores for anxiety, depression, mood change, daily functioning and other quality-of-life parameters did not differ between CVAP and docetaxel treatment.