Between June 1996 and March 1998, 429 first-line metastatic breast
cancer patients were randomized to receive AT (doxorubicin
[Adriamycin] 50 mg/m² and docetaxel [Taxotere] 75 mg/m²) or
AC (doxorubicin 60 mg/m² and cyclophosphamide [Cytoxan, Neosar]
600 mg/m²), day 1 every 3 weeks for a maximum of eight cycles.
Granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen])
was not allowed, except after a prior febrile neutropenic
complication. Eligible patients were required to have metastatic
disease with measurable or evaluable lesions. No prior chemotherapy
(CT) for metastatic breast cancer was allowed; prior nonanthracycline
adjuvant CT was allowed.
Baseline characteristics were well balanced. Overall, patients had a
median age of 53, a median Karnofsky performance status of 90, and a
median disease-free interval of 25 months; 42% of patients had had
adjuvant CT. The following organs were involved: visceral 63%, bone
54%; 41% of patients had three or more organs involved. The main
reasons for discontinuing treatment were as follows: reaching eight
cycles, 49% (AT) vs 36% (AC); progressive disease, 21% (AT) vs 32%
(AC); toxicity, 13% (AT) vs 13% (AC). The median number of cycles was
8 (AT) vs 7 (AC). Median cumulative dose of doxorubicin (CDA) was 378
mg/m² (AT) vs 420 mg/m² (AC). Median relative dose
intensity (RDI) was 96% (AT) vs 96% (AC).
Severe (National Cancer Institute grade 3/4) events occurring in ³
1% of cycles included neutropenia, 82% (AT) vs 69% (AC); febrile
neutropenia, 7% (AT) vs 2% (AC); anemia, 3% (AT) vs 4% (AC);
infection, 1% (AT) vs < 1% (AC); nausea, 1% (AT) vs 1% (AC);
vomiting, 1% (AT) vs 1% (AC); stomatitis, 1% (AT) vs 1% (AC);
diarrhea, 1% (AT) vs < 1% (AC). Severe asthenia was seen in 8%
(AT) vs 3% (AC) of patients; severe edema was seen in 1% (AT) vs 0%
(AC) of patients.
Left ventricular ejection fraction decrease ³
30 points from baseline occurred in 1% (AT) vs 6% (AC) of evaluable
patients. Clinical congestive heart failure (CHF) was seen in 3% (AT)
vs 4% (AC) of patients. The CDA was > 360 mg/m² in 54% (AT)
vs 64% (AC) of patients. Toxic deaths occurred in 1 AT patient (CHF)
and 4 AC patients (1 sepsis, 3 CHF). As of April 1999, the median
follow-up is 18 months.
CONCLUSION: AT shows superior efficacy over standard AC in metastatic
breast cancer, despite a lower dose intensity of doxorubicin.
Neutropenia and its complications were higher in AT but did not
compromise RDI. Other toxicities were similar in both arms. The AT
advantage is also being tested in early breast cancer.