HOUSTON—A study comparing eight cycles of adjuvant fluorouracil(Drug information on fluorouracil), doxorubicin, and cyclophosphamide(Drug information on cyclophosphamide) (FAC) to four cycles of paclitaxel(Drug information on paclitaxel) (Taxol) followed by four cycles of FAC in women with operable breast cancer showed a nonsignificant trend toward benefit from the paclitaxel/FAC regimen.
Preliminary data from work by investigators at the University of Texas M.D. Anderson Cancer Center were presented at the ASCO annual meeting by Eve Thomas, MD.
Between May 1994 and June 1998, 524 patients with operable T1-3, N0-1, M0 breast cancer were treated in this prospective randomized trial, Dr. Thomas reported. Two-thirds of the patients had T2 or larger tumors.
Patients were randomized to either eight cycles of FAC (n = 259) or four cycles of paclitaxel (250 mg/m² administered as a 24-hour infusion every 3 weeks) followed by four cycles of FAC (n = 266). Dr. Thomas said that the researchers initially did not include growth factor support or prophylactic antibiotics, but, due to a high incidence of febrile neutropenia, these approaches were used in the later part of the study.
Patients with an intact primary tumor received the first four cycles preoperatively (n = 174), and patients referred after surgery received all cycles as adjuvant therapy (n = 350). At completion of chemotherapy, local radiation therapy was administered if clinically indicated.
Estrogen-receptor (ER)–positive patients age 50 and older also received 5 years of tamoxifen(Drug information on tamoxifen) (Nolvadex).
Reducing Recurrence Risk
The median follow-up for all patients is 43.5 months. Intent-to-treat analysis has shown 38 recurrences in the patients treated with FAC alone and 28 recurrences with paclitaxel followed by FAC.
“An estimated 24% reduction in the risk of recurrence in patients who receive FAC after paclitaxel was observed,” Dr. Thomas reported. “There was a trend toward lower recurrence on the paclitaxel/FAC arm, regardless of ER status,” Dr. Thomas observed, although the difference was not significant, perhaps due to the small sample size.
Is Study Underpowered?
Discussing the study (along with other adjuvant papers), Kathy S. Albain, MD, of Loyola University Medical Center, Chicago, noted, “In this well-conducted but small, perhaps underpowered adjuvant study, women were not selected for age or receptor status. There was no significant difference in disease-free or overall survival regardless of whether FAC was given for eight cycles or for four cycles but preceded by four cycles of paclitaxel. The duration of therapy in both arms was 24 weeks. Therefore, either the study is underpowered to detect a true taxane benefit, or both regimens are equally effective at this longer duration.”
In the context of other related studies, Dr. Albain said that all adjuvant therapy may not be equal, “except perhaps when addressing lower-risk subsets. If the risk of recurrence is low, it may not matter which type of chemotherapy is selected. However, tumor size, nodal status, proliferative rate, HER2 status and other biomarkers may affect this decision. If there is a higher risk of recurrence, a 24-week anthracycline-containing regimen with or without a taxane is preferred.”
