Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancer.
OBJECTIVE
In most neoadjuvant chemotherapy regimens, the taxane is administered either in combination with an anthracycline or after an anthracycline-containing regimen. We sought to test the feasibility, safety, and determine the pathological complete response (pCR) rate of administering docetaxel first followed by epirubicin as neoadjuvant chemotherapy in women with clinical stage II, III breast cancer.


METHODS
Twenty-five women with newly diagnosed clinical stage IIB (n = 10), IIIA (n = 5), or IIIB (n = 10) received 3 cycles of docetaxel 100 mg/M2 intravenously (IV) every 3 weeks followed by 3 cycles of epirubicin 100 mg/M2 IV every 3 weeks. pCR was defined as the absence of invasive cancer in the breast at definitive surgery.


RESULTS
The median primary tumor size was 6 cm (range 1-12 cm), and 13 (52%) women had clinically palpable axillary lymph nodes. Patients received 149 of the 150 planned cycles of docetaxel and epirubicin without treatment delays, and only 3 (12%) patients had a dose reduction of docetaxel. Seven (28%) patients experienced febrile neutropenia, and 9 (36%) patients had grade 3 non-hematological toxicities with diarrhea being the most frequent in 3 (12%) patients. Six (24%) patients had pCR in the breast. Analysis of pre- and post-docetaxel biopsies from a subset of patients documented taxane-induced activation of mitogen-activated and stress-activated protein kinase pathways.


CONCLUSIONS
Neoadjuvant docetaxel followed by epirubicin is well tolerated and active in breast cancer. To our knowledge, this is first description of docetaxel-induced activation of mitogen-activated and stress-activated protein kinase pathways in human breast cancer.
Ramaswamy
Bhuvaneswari
B
Division of Hematology/Oncology and Comprehensive Breast Health Services, Ohio State University Medical Center, Columbus, OH, USA.
Povoski
Steven P
SP
Rhoades
Chris
C
Allen
Joan
J
Hauger
Marsha
M
Young
Donn
D
Burak
William
W
Farrar
William
W
Yee
Lisa
L
Kendra
Kari
K
Somasundaram
Sivagurunathan
S
Orlowski
Robert Z
RZ
Shapiro
Charles L
CL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin