TY - JOUR
T1 - Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancer
AU - Ramaswamy, Bhuvaneswari
AU - Povoski, Steven P.
AU - Rhoades, Chris
AU - Allen, Joan
AU - Hauger, Marsha
AU - Young, Donn
AU - Burak, William
AU - Farrar, William
AU - Yee, Lisa
AU - Kendra, Kari
AU - Somasundaram, Sivagurunathan
AU - Orlowski, Robert Z.
AU - Shapiro, Charles L.
PY - 2005/9
Y1 - 2005/9
N2 - Purpose. 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. Patients and 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. Conclusion. 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.
AB - Purpose. 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. Patients and 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. Conclusion. 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.
KW - Docetaxel
KW - MAPK pathway activation
KW - Neoadjurant
UR - http://www.scopus.com/inward/record.url?scp=25144446227&partnerID=8YFLogxK
U2 - 10.1007/s10549-005-3784-z
DO - 10.1007/s10549-005-3784-z
M3 - Article
C2 - 16184461
AN - SCOPUS:25144446227
SN - 0167-6806
VL - 93
SP - 67
EP - 74
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -