HOUSTONA study comparing eight cycles of adjuvant fluorouracil,
doxorubicin, and cyclophosphamide (FAC) to four cycles of paclitaxel
(Taxol) followed by four cycles of FAC in women with operable breast
cancer showed a nonsignificant trend toward benefit from the
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
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
Estrogen-receptor (ER)positive patients age 50 and older also
received 5 years of 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.