Originally published as JCO Early Release 10.1200/JCO.2008.20.3133 on April 13 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Untch, M. Articles by Konecny, G. E. PubMed PubMed Citation Articles by Untch, M. Articles by Konecny, G. E. Social Bookmarking                            What's this?

Intensive Dose-Dense Compared With Conventionally Scheduled Preoperative Chemotherapy for High-Risk Primary Breast Cancer

From the Helios Klinikum, Campus Berlin Buch, Berlin; Klinikum Frankfurt Höchst, Frankfurt; Bethesda Krankenhaus, Mönchengladbach; University of Halle (Saale), Halle (Saale); Klinikum Landshut, Landshut; Technical University of Munich; Klinikum Grosshadern, University of Munich, Munich; University of Cologne, Cologne; Frauenklinik, Evangelisches Bethesda Krankenhaus, Duisburg; University of Hamburg-Eppendorf, Hamburg; University of Heidelberg, Heidelberg; Städtisches Klinikum, Wolfsburg; University of Tübingen, Tübingen; University of Ulm, Ulm; University of Marburg, Marburg; Gynäkologisch-Onkologische Praxis, Hannover; Wissenschaftlicher Service Pharma, Langenfeld, Germany; and David Geffen School of Medicine, University of California, Los Angeles, CA.

Corresponding author: Gottfried E. Konecny, MD, David Geffen School of Medicine, University of California Los Angeles, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA 90404-2429; e-mail: gkonecny{at}mednet.ucla.edu.

Purpose To compare preoperative intense dose-dense (IDD) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer (BC).

Patients and Methods In this randomized phase III trial a total of 668 eligible primary BC patients stratified for tumors 3 cm (n = 567) or inflammatory BC (n = 101) were randomly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks. All patients received three cycles of cyclophosphamide, methotrexate, and fluorouracil chemotherapy after surgery.

Results IDD treatment significantly improved pathologic complete response rate (18% v 10%; odds ratio [OR] 1.89; P = .008), disease-free survival (DFS; hazard ratio [HR], 0.71; P = .011), and overall survival (OS; HR, 0.83; P = .041) compared to epirubicin/paclitaxel. Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial (DFS HR, 1.10; P = .739; OS HR, 1.25; P = .544). In contrast, patients with noninflammatory BC significantly benefited from IDD treatment (DFS HR, 0.65, P = .005; OS HR, 0.77, P = .013). Treatment effects in multivariate analysis were significant for noninflammatory BC (DFS HR, 0.65, P = .015; OS HR, 0.79, P = .034), but not for all patients (DFS HR, 0.76; P = .088; OS HR, 0.82; P = .059). IDD therapy was associated with significantly more nonhematologic toxicities, anemia, and thrombocytopenia, but with similar neutropenia and infection rates.

Conclusion Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy. IDD was less well tolerated compared to standard treatment, but improved clinical outcomes in patients with noninflammatory high-risk primary BC.

Supported by Amgen, Bristol- Myers Squibb, and Pfizer, Germany.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL.

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?