Review - Haymarket Media Group

Figure
Paclitaxel 175 mg/m2
every 21 days for 4 doses
n=1253
Randomization scheme.
Trial Design
Eligible patients had operable, histologically confirmed
adenocarcinoma of the breast with histologically
involved lymph nodes (tumor stage T1, T2, or
T3 and nodal stage N1 or N2) or high-risk, axillary
lymph node–negative disease (T2 or T3, N0) without
distant metastases. Adequate organ function was
required. Exclusion criteria included history of
myocardial infarction, congestive heart failure, heart
disease, pregnancy, or history of hypersensitivity
reaction to paclitaxel or docetaxel. Full inclusion and
exclusion criteria can be found online in the supplementary
appendix of the original article.
A total of 5052 patients were enrolled, of whom
4950 (98%) were eligible. All patients received doxorubicin
(60 mg/m 2 of body surface area) and
cyclophosphamide (600 mg/m 2 of body surface area)
every 3 weeks for four cycles. Patients were then randomized
to one of four treatment arms (Figure).
Women who had breast-sparing surgery received
radiotherapy according to accepted standards of care,
and patients who had a modified radical mastectomy
received radiotherapy at the discretion of the treating
physician. All women with hormone receptor–
positive disease received tamoxifen 20 mg daily for 5
years. The protocol was modified in 2005 to allow for
a change to an aromatase inhibitor prior to completion
of 5 years of tamoxifen or to begin an aromatase
inhibitor after completing 5 years of tamoxifen.
Operable breast cancer,
lymph node positive or high-risk node negative
N=4950
Doxorubicin 60 mg/m 2 +
cyclophosphamide 600 mg/m2
every 21 days for 4 cycles
Paclitaxel 80 mg/m2
weekly for 12 doses
n=1231
Docetaxel 100 mg/m2
every 21 days for 4 doses
n=1236
Weekly paclitaxel and breast cancer
Docetaxel 35 mg/m2
every 21 days for 12 doses
n=1230
The primary end point of the study was diseasefree
survival, which was defined as the time from
randomization to disease recurrence and included
death from recurrence, death without recurrence,
and contralateral breast cancer. The study had 86%
power to detect a 17.5% reduction in the hazard
rate for failure among the docetaxel groups or with
weekly instead of every-3-week dosing. All eligi-
The primary end point
of the study was
disease-free survival.
ble patients undergoing randomization were
included in the efficacy analysis, and all treated
patients were included in the adverse events
analysis. The log-rank test was used for analysis
of disease-free and overall survival. Kaplan-Meier
analysis was used to estimate distributions of
events with respect to time. Cox proportional hazards
models were used to estimate hazard ratios
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