Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancer

Bhuvaneswari Ramaswamy, Steven P. Povoski, Chris Rhoades, Joan Allen, Marsha Hauger, Donn Young, William Burak, William Farrar, Lisa Yee, Kari Kendra, Sivagurunathan Somasundaram, Robert Z. Orlowski, Charles L. Shapiro

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalBreast Cancer Research and Treatment
Volume93
Issue number1
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Docetaxel
  • MAPK pathway activation
  • Neoadjurant

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