FLORENCE, ItalyBoosting both the dose intensity and dose
density of adjuvant chemotherapy significantly prolongs survival in
women with high-risk breast cancer, according to a multicenter trial
presented at the First European Breast Cancer Conference. A
twofold dose increase in epirubicin is possible with G-CSF [Neupogen]
support, said Dr. G. Konecny of the University of Munich.
It is a feasible outpatient treatment, quality of life is good
during treatment, and treatment duration is especially short.
The trial recruited 182 breast cancer patients between the ages of 18
and 65 who either had at least 10 positive nodes or extracapsular
involvement, or both. In such patients, Dr. Konecny said, the outcome
following standard cyclophosphamide/methotrexate/fluorouracil (CMF)
treatment is usually disastrous.
Study participants were randomly assigned to either four biweekly
cycles of dose-intensified epirubicin/cyclophosphamide (DI-EC),
120/600 mg/m² on days 2 to 12, with G-CSF support, or to four
triweekly cycles of EC, 90/600 mg/m², followed by three cycles
of CMF, 500/40/600 mg/m².
We included two concepts in our scheduleincreasing the
dose intensity by increasing the epirubicin dose from 90 to 120 mg/m2,
and increasing the dose density by shortening the intervals between
treatments, Dr. Konecny said. All patients underwent
radiotherapy as well, and those with estrogen-receptor-positive
tumors also received tamoxifen (Nolvadex) after chemotherapy.
The investigators were able to reach 92% of the planned dose
intensity with the DI-EC regimen and 97% of the planned dose
intensity with EC/CMF therapy. The total duration of chemotherapy,
however, was only 7.6 weeks in the dose-intensified arm, compared
with 24 weeks in the standard arm.
We achieved a mean disease-free survival of 37 months with
standard CMF therapy and 44 months with intensified therapy, and this
difference was significant, Dr. Konecny reported.
He observed that, after a median follow-up of 24 months, only 13 of
91 women treated with dose-intense, dose-dense therapy experienced a
recurrence, compared with 25 of 83 patients who received standard
therapy. The follow-up period was too short to demonstrate an
improvement in overall survival, however.
Dr. Konecny and his colleagues also confirmed that c-erbB2 (also
known as HER2) overexpression had a detrimental impact on survival.
In contrast to previous reports, however, c-erbB2-positive patients
benefited less from anthracycline dose intensification than did their
Patients assigned to dose-intensified therapy with G-CSF support
actually showed higher mean white blood cell counts than those
treated with standard therapy. However, platelet counts were lower
and anemia was more frequent in the dose-intensified arm.