NEW YORKThe jury may still be out on the value of adjuvant paclitaxel(Drug information on paclitaxel) (Taxol) for early breast cancer (see article on page 3 on the updated NCCN breast cancer guideline), but a study from M.D. Anderson suggests it may have a small advantage over conventional chemotherapy. In this phase III trial, 524 patients with early breast cancer were randomized to receive either eight cycles of fluorouracil(Drug information on fluorouracil) (5-FU), doxorubicin, and cyclophosphamide(Drug information on cyclophosphamide) (FAC) or four cycles of paclitaxel followed by four cycles of FAC.
"This trial showed that the antitumor activity of paclitaxel is clinically comparable to the FAC combination," said Aman U. Buzdar, MD, professor of medicine and deputy chairman of the Department of Breast Medical Oncology, M.D. Anderson Cancer Center.
Dr. Buzdar presented preliminary results of the study, which was completed in 1998. "It has been established that paclitaxel as a single agent has substantial antitumor activity," Dr. Buzdar said at the Chemotherapy Foundation Symposium XVIII. "Based on this, we wanted to evaluate adding paclitaxel to FAC as a means of altering the natural history of the disease."
The trial enrolled patients with operable TNM stage I-IIB breast cancer (T1-3, N0-1, M0). One arm received eight cycles of FAC in the standard M.D. Anderson regimen: a 500 mg/m2 IV bolus of cyclophosphamide on day 1, a 500 mg/m2 IV bolus of 5-FU on days 1 and 4; and 50 mg/m2 continuous infusion of doxorubicin(Drug information on doxorubicin) over 72 hours on days 1 to 3. The other arm received four cycles of paclitaxel at a dose of 250 mg/m2 as a 24-hour infusion every 3 weeks followed by four cycles of FAC in the standard dose.
About one third of patients had intact primary tumors; these received the first four cycles of chemotherapy preoperatively. The balance (350 patients) had surgery prior to systemic therapy and received all eight cycles as adjuvant chemotherapy. Estrogen-receptor (ER) status was divided equally between negative and positive in the two arms. ER-positive patients who were 50 years of age or over were given 5 years of tamoxifen(Drug information on tamoxifen) following chemotherapy.
Median follow-up was 43.5 months. Disease-free survival at 4 years was 81.5% on FAC alone vs 85.2% with pacli-taxel plus FAC, but the difference did not reach statistical significance (P = .2). Dr. Buzdar said that the small size of the study group may account for the lack of statistical significance in this measure.
He cited a larger trial, CALGB-9344, that showed a significant survival advantage for paclitaxel over AC (doxorubicin, cyclophosphamide). However, the results have been questioned because one arm received only four cycles of chemotherapy (AC) while the other received eight, including paclitaxel.
"In our study, both cohorts received eight cycles of chemotherapy, the only difference being administration of paclitaxel," Dr. Buzdar said. "The reduction in risk of recurrence is more likely to be related to the addition of paclitaxel than the duration of therapy."
In the M.D. Anderson study, Dr. Buzdar said, there is a trend toward a reduced risk of recurrence, regardless of ER status, when paclitaxel is added to FAC. He added that the impact on survival remains to be defined.
When asked how he would respond to the recent NIH consensus statement that there is no established role for paclitaxel in the adjuvant setting, he said he has serious reservations about consensus statements in general and this one in particular.
"Consensus is based on the lowest denominator," Dr. Buzdar said. "The panel has no expertise in the treatment of breast cancer. You have people sitting on that panel who have never seen a breast cancer." He concluded by saying: "The data are there; you can make up your own mind."