Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study.
OBJECTIVE
To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer.


METHODS
Patients (tumor size > or = 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m(2), either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment.


RESULTS
Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of -1.2% in favor of ADoc, with a 95% confidence interval of -8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status.


CONCLUSIONS
A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.
von Minckwitz
G
G
Department of Gynecology and Obstetrics, Goethe University, Frankfurt am Main, Germany. minckwitz@em.uni-frankfurt.de
Costa
S D
SD
Raab
G
G
Blohmer
J U
JU
Eidtmann
H
H
Hilfrich
J
J
Merkle
E
E
Jackisch
C
C
Gademann
G
G
Tulusan
A H
AH
Eiermann
W
W
Graf
E
E
Kaufmann
M
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010349:Patient Compliance; D011300:Preoperative Care; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids
D043823:Taxoids; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel