Between April 1998 and June 1999 the German Adjuvant Breast Cancer
Group (GABG) enrolled 250 patients from 56 centers, with core-cut
biopsyconfirmed unilateral bidimensional measurable operable
breast cancer (T > 3 cm, N0-2, M0), into the GEPARDO (German
Preoperative Adriamycin Docetaxel) trial. Patients were randomized to
receive four cycles of dose-intensified doxorubicin (50 mg/m²)
and docetaxel (Taxotere) (75 mg/m²) every 14 days, including
granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen])
support on days 610, with or without tamoxifen (Nolvadex) 30
mg/d, as primary systemic therapy.
The aim was to investigate the tamoxifen-induced drug resistance
modulating effect on pathologic complete response (pCR = no invasive
or in situ viable tumor cells). After surgery, all patients were
given tamoxifen 30 mg/d as an adjuvant, planned for 5 years. Tumor
size and shrinkage were assessed at study entry clinically, by
mammography, ultrasound, and optionally by MRI. Before surgery the
method that revealed optimal tumor assessment had to be repeated.
A total of 122 patients were randomized to receive
doxorubicin/docetaxel plus tamoxifen, and 128 to receive doxorubicin/docetaxel
alone. Median age at entry was 48 years (range: 2767 years).
Tumor size was > 4 cm by palpation in 41% of patients; 51% were
clinically node negative. Estrogen-receptor status could be analyzed
in 196 patients, 59% of whom were positive. These factors were well
balanced between the two treatment arms. 247 patients were evaluable
for the extent of surgery and for tumor response.
Breast-conserving surgery was performed in 68.6% (83/121 patients)
with doxorubicin/docetaxel plus tamoxifen and in 69.8% (88/126) with
doxorubicin/docetaxel alone (95% CI for difference: -12.8%, 10.3%).
The rate of pCR was 9.1% (11/121) with doxorubicin/docetaxel plus
tamoxifen and 10.3% (13/126) with doxorubicin/docetaxel (95% CI for
difference: -8.6%, 6.2%).
CONCLUSION: Dose-intensified preoperative doxorubicin/docetaxel with
or without tamoxifen achieved a high rate of breast-conserving
surgery and a good pCR rate, but showed no difference in the two
treatment arms. The regimen is feasible with moderate toxicity.