Paclitaxel-Doxorubicin Effective as Neoadjuvant Chemotherapy

PARIS—Neoadjvant chemotherapy with the combination of paclitaxel (Taxol) and doxorubicin gave a pathologic complete response rate of 16% in a phase II randomized multicenter French clinical trial of women with previously untreated breast cancers.

Patients treated with the taxane combination had higher pathologic and clinical response rates than patients given the combination of doxorubicin (Adriamycin) and cyclophosphamide (AC).

Additionally, more patients treated with paclitaxel and doxorubicin qualified for breast-conserving surgery, compared with patients in the doxorubicin-cyclophosphamide arm.

“The combination of paclitaxel and doxorubicin is clinically active in the neoadjuvant setting,” Veronique Dieras, MD, a breast cancer specialist in the medical oncology service at the Curie Institute, said at a general session of the 21st Annual San Antonio Breast Cancer Symposium.

She noted that a number of issues still must be resolved. “We need to improve the pathologic response rate, since that is a more reliable indicator of outcome. We also need to identify critical factors associated with response so that we can optimize therapy. However, the results we obtained with this combination are encouraging.”

Dr. Dieras reported data from a trial that had as its primary objective pathologic complete response rate for each neoadjuvant combination therapy, as determined prior to definitive surgery and radiation therapy.

Secondary objectives included the objective clinical response rate, disease-free survival, and overall survival. Dr. Dieras reported data on pathologic and clinical response rates.

The trial included patients who had stage T2-3, N0-1, M0 previously untreated breast cancer. Patients were stratified according to center and tumor size (T2 or T3).

Randomization

Investigators randomized the patients to one of two neoadjuvant regimens: doxorubicin 60 mg/m² as an IV bolus followed by paclitaxel 200 mg/m² as a 3-hour infusion, or the same dose of doxorubicin plus cyclophosphamide 600 mg/m² IV bolus.

Patients were randomized in a 2:1 ratio to the paclitaxel-containing combination vs the combination containing cyclophosphamide. Treatment was repeated every 3 weeks for a total of four cycles, followed by surgery, then radiotherapy.

The trial design incorporated an interim analysis that allowed for termination if specific endpoint criteria were met: fewer than three complete pathologic responses in the first 40 patients enrolled in the cyclophosphamide arm or fewer than seven complete responses in the first 80 patients enrolled in the paclitaxel arm. Without premature termination, investigators planned to enroll a total of 240 patients (160 receiving doxorubicin-paclitaxel and 80 receiving AC).

The trial was terminated after the interim analysis showed only two pathologic complete responses in the cyclophosphamide cohort. In contrast, 11 of the initial 80 paclitaxel-treated patients had a complete response.

Dr. Dieras reported findings in a total of 200 patients, 67 randomized to the doxorubicin-cyclophospha-mide regimen and 133 treated with doxorubicin-paclitaxel.

Pathologic complete responses occurred in 16% of the doxorubicin-paclitaxel group, compared with 10% of the doxorubicin-cyclophosphamide cohort. The definition of complete response encompassed no evidence of residual disease (6% with paclitaxel and 4% with cyclophosphamide), noninvasive residual cancer, or ductal carcinoma in situ (DCIS).

Objective clinical responses occurred in 85% of the doxorubicin-paclitaxel group, including complete responses in 18%. In the doxorubicin-cyclophosphamide cohort, the overall response rate was 66%, including complete responses in 6% of patients.

Treatment with doxorubicin-paclitaxel led to conservative breast surgery in 58% of cases, compared with 45% of patients in the doxorubicin-cyclophosphamide arm.

“These results are encouraging and will provide the basis for further investigation of the combination of paclitaxel and doxorubicin in the neoadjuvant setting,” Dr. Dieras said.