Paclitaxel Seems Equivalent to FAC as Neoadjuvant Chemo

SAN ANTONIO—Preliminary results from an ongoing clinical trial suggest that neoadjuvant chemotherapy of breast cancer with paclitaxel (Taxol) alone produces response rates comparable to those achieved with the three-drug FAC (fluorouracil, Adriamycin, cyclophosphamide) regimen.

Speaking at a satellite symposium held in conjunction with the 21st Annual San Antonio Breast Cancer Symposium, Aman Buzdar, MD, expressed optimism for neoadjuvant use of paclitaxel, but he cautioned that the 23-month follow-up is too brief to draw definitive conclusions. “With longer follow-up, we will know the true value of paclitaxel in neoadjuvant breast cancer therapy,” said Dr. Buzdar, a breast medical oncologist at M.D. Anderson Cancer Center.

The current trial has its origin in an M.D. Anderson study of 25 patients with metastatic disease treated with paclitaxel. The treatment led to objective responses in two-thirds of patients, including complete responses in 12%. Only one patient failed to achieve at least a minor response, Dr. Buzdar said.

Results of this small-scale evaluation subsequently were confirmed in a similar study at Memorial Sloan-Kettering Cancer Center. Almost three-fourths of 26 patients had major responses, including complete responses in 12%.

174 Patients Randomized

“On the basis of these encouraging results, we decided to put paclitaxel to the test in a neoadjuvant fashion to see what the effect would be on cytoreduction and antitumor activity,” Dr. Buzdar said.

Between 1994 and the middle of 1998, investigators randomized 174 patients to paclitaxel monotherapy or to neoadjuvant treatment with conventional FAC.

Paclitaxel was administered at a dose of 250 mg/m²—the same dose used to treat metastatic breast cancer. Treatment was repeated every 3 weeks for four cycles, followed by surgery, an additional four cycles of FAC, and radiation therapy. Patients older than 50 years also will receive tamoxifen (Nolvadex) for 5 years.

Patients in the two treatment groups had identical 79.3% overall response rates. Paclitaxel led to complete re-sponses in 26.4% of patients vs 24.1% with FAC. FAC resulted in more patients with no evidence of residual disease (17.2% vs 5.7%), whereas more pacli-taxel-treated patients had DCIS only (8% vs 4.6%) or minimal residual disease (26.4% vs 11.5%) after neoadjuvant therapy. Dr. Buzdar also noted that paclitaxel treatment was associated with a higher rate of breast-conserving surgery, 46% vs 37% for patients receiving FAC.

At a median follow-up of 23 months, patients in the paclitaxel cohort had superior disease-free survival rates at 1 year (100% vs 94%) and 2 years (94% vs 89%). Dr. Buzdar emphasized that longer follow-up is needed to provide a true indication of the impact of the two neoadjuvant regimens on survival.