Originally published as JCO Early Release 10.1200/JCO.2007.14.3941 on March 3 2008

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Randomized Phase II Adjuvant Trial of Dose-Dense Docetaxel Before or After Doxorubicin Plus Cyclophosphamide in Axillary Node-Positive Breast Cancer

Shannon Puhalla, Ewa Mrozek, Donn Young, Susan Ottman, Anne McVey, Kari Kendra, Nancy J. Merriman, Mark Knapp, Taral Patel, Mark E. Thompson, James F. Maher, Timothy D. Moore, Charles L. Shapiro

From the Ohio State University Medical Center and Comprehensive Breast Health Services; Clinical Trials Office of the Comprehensive Cancer Center; Department of Psychiatry, The Ohio State University; Mid-Ohio Oncology/Hematology Inc, Columbus; Oncology Partners Network, Cincinnati, OH

Corresponding author: Charles L. Shapiro, MD, Ohio State University, Arthur James Cancer Hospital & Research Institute, 320 W 10th St, Starling-Loving Hall, B421, Columbus, OH 43210; e-mail: charles.shapiro{at}osumc.edu

Purpose: An anthracycline-based combination followed by, or combined with, a taxane is the sequence used in most adjuvant chemotherapy regimens. We hypothesized that administering the taxane before the anthracycline combination would be associated with fewer dose reductions and delays than the reverse sequence. To test this hypothesis, a randomized phase II multicenter adjuvant chemotherapy trial was performed.

Patients and Methods: Fifty-six patients with axillary node-positive, nonmetastatic breast cancer were randomly assigned either to group A (docetaxel [DOC] 75 mg/m² intravenously [IV] every 14 days for four cycles followed by doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² [AC] IV every 14 days for four cycles); or to group B (AC followed by DOC) at the identical doses and schedule. Pegfilgrastim 6 mg subcutaneous injection was administered 1 day after the chemotherapy in all treatment cycles. The primary objective was to administer DOC without dose reductions or delays before or after AC and calculate the relative dose intensity (RDI) of DOC and AC.

Results: The majority of toxicities were grade 0 to 2 irrespective of sequence. The RDI for DOC was 0.96 and 0.82, respectively, in groups A (DOC followed by AC) and B (AC followed by DOC), with more frequent dose reductions occurring in group B (46% v 18%). The RDI for AC was 0.95 and 0.98 in groups A and B, respectively.

Conclusion: The administration of DOC before AC results in fewer DOC dose reductions and a higher RDI than the reverse sequence. Larger trials evaluating the sequence of DOC before anthracyclines are justified.

published online ahead of print at www.jco.org on March 3, 2008.

Supported by a research grant from Sanofi-Aventis. Data management support by BridgeSite Clinical Research, Columbus, OH. Charles L. Shapiro was the recipient of an unrestricted educational grant from Sanofi-Aventis to support a breast cancer fellowship.

Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, TX, December 14-17, 2006.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.