The results of a multicenter, phase III metastatic breast cancer
study indicates that, in women with previously untreated metastatic
breast cancer, sequential chemotherapy induction using doxorubicin
and docetaxel (Taxotere) is as effective and safe as standard
simultaneous induction but does not improve the response to
treatment. These results were presented by Response Oncology, Inc., a
comprehensive cancer management company based in Memphis, at the 36th
Annual Meeting of the American Society of Clinical Oncology (ASCO).
The study included 98 newly diagnosed patients. One group received
the standard doxorubicin/docetaxel combination schedule in which the
drugs were given simultaneously every 21 days. The second group was
given a dose-dense sequential schedulea maximal dose of
doxorubicin with minimum cycle length prior to delivery of docetaxel,
which was administered in the same fashion.
Following induction, stable and responding patients received
high-dose consolidation therapy with stem-cell support. The overall
response rate at the end of induction was similar for both the
simultaneous and sequential induction groups: 66% and 65%,
The two treatments were equally safe and well tolerated. However, the
simultaneous induction schedule produced a higher rate of
neutropenia, whereas the sequential schedule resulted in a higher
rate of anemia and skin reaction.
The trial included women with previously untreated stage IV breast
cancer who had received a prior cumulative doxorubicin dose of 300
mg/m² or less. Participants ranged from 18 to 65 years of age
with an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 to 1. All patients had measurable disease.
Women who had failed doxorubicin treatment within the last 12 months
and/or had undergone prior taxane treatment were excluded. At the
time of their diagnosis, 37% of the women had metastatic disease and
54% had undergone prior adjuvant therapy. The disease had spread to
the liver in 31%.
The simultaneous induction group received both doxorubicin, 45
mg/m², and docetaxel, 75 mg/m², administered intravenously
every 21 days for four treatment cycles. The sequential induction
group received 90 mg/m² of doxorubicin intravenously every 14
days for two treatment cycles followed by 100 mg/m² of docetaxel
administered intravenously every 21 days for three cycles.
Response was assessed 3 to 4 weeks after induction. The complete
response to simultaneous induction was 28%, compared with 18% in the
sequential induction group. The partial response rates were 45% and
Among patients in the simultaneous induction group, 16% had stable
disease at follow-up, and 11% had disease progression. The rates of
stable disease and disease progression in the sequential induction
group were 21% and 10%, respectively. There were no significant
differences between the two treatment groups in any of the response measures.
The most common side effect was neutropenia, which occurred more
often in the simultaneous arm (67% vs 34%) due to the differences in
the support medications. Gastrointestinal, neurologic, infectious,
and hyperglycemic side effects occurred equally in both groups. Skin
reactions occurred more frequently in the sequential arm of the study.
The median delivered dose intensity and cumulative dose were similar
in the two treatment arms. However, median dose density was markedly
higher for the sequential arm.
It has been suggested that the dose-dense schedule may improve the
results of chemotherapy in women with metastatic breast cancer.
Our findings indicate that combination chemotherapy with
doxorubicin and docetaxel is effective and well tolerated with both
induction schedules, said Lee S. Schwartzberg, MD, associate
scientific officer of Response Oncology, Inc. Sequential
induction does not offer any advantages over conventional induction
treatment in these patients.