Nonanthracycline Combination Shows Promise as Neoadjuvant Therapy for Breast Cancer

MIAMI—As neoadjuvant therapy for breast cancer, docetaxel (Taxotere) plus cisplatin delivers pathologic complete response rates as good or better than standard anthracycline-containing regimens, results of a nonrandomized study suggest. The study involved 57 patients with locally advanced and inflammatory breast cancer.

The pathologic complete response rate of 27% in this trial "is very unusual," considering the large median tumor size (9 cm, range 4 to 37 cm) and inclusion of women with inoperable breast cancer (about 50% of the patients) and inflammatory disease (about 25% of the patients), according to Young Lee, MD, of the Sylvester Cancer Center, University of Miami.

The favorable rate may be due to synergistic activity between platinums and taxanes, Dr. Lee noted. In previous studies, docetaxel alone produced a pathologic complete response of only about 7%.

‘Very Good’ Survival

Investigators treated 57 black, Latin, and Caribbean women. The median age was 49 and 53% of the women were premenopausal. Patients received cisplatin 70 mg/m² and docetaxel 70 mg/m², with G-CSF prophylaxis, every 21 days for four cycles. This was followed by surgery, then adjuvant doxorubicin/cyclophosphamide (Cytoxan, Neosar) for four cycles, and radiation therapy. Women who were estrogen receptor-positive (20 of 56 evaluable patients, or 36%) received 20 mg tamoxifen daily.

Pathologic complete response in the breast to neoadjuvant treatment was seen in 15 of 56 evaluable patients (27%); 11 patients (20%) had pathologic complete response in both breast and axilla.

Overall survival at 3 years was 78%, and disease-free survival was 69%, both considered "very good" in this high-risk group. Overall survival was 92% for women who had a pathologic complete response in the breast and 74% for women who did not.

Similar Toxicity Profiles

Grade 3/4 toxicity in the neoadjuvant docetaxel/cisplatin phase of the trial included leukopenia in three patients (5%) and anemia in one patient (2%). With adjuvant doxorubicin/cyclophosphamide, leukopenia occurred in seven patients (12%).

The most common nonhematologic toxicity was grade 1/2 alopecia, experienced by 100% of patients in both the neoadjuvant and adjuvant regimens. Hyperglycemia occurred in 24 patients during the docetaxel/cisplatin neoadjuvant phase of the trial; six of the cases were grade 3/4.

"We do see some degree of myelosuppresion, and there is alopecia, but otherwise it is pretty much the same toxicity profile" as one might expect from a doxorubicin/cyclophosphamide regimen, Dr. Lee said. She expressed hope that oncologists will "consider docetaxel plus cisplatin as an alternative to the Adriamycin-based chemotherapy that many still use in the preoperative setting."

Investigators are currently evaluating a weekly docetaxel/carboplatin (Paraplatin) regimen as another potential alternative to anthracycline-based neoadjuvant therapy for locally advanced and inflammatory breast cancer. "So far, the combination is very promising," Dr. Lee said. The results are expected to be reported at the 2003 meeting of the American Society of Clinical Oncology.