Open Access Research article

FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients

Peter A Fasching1*, Sebastian M Jud1, Maik Hauschild2, Sherko Kümmel3, Martin Schütte4, Matthias Warm56, Volker Hanf7, Dieter Grab8, Jutta Krocker9, Elmar Stickeler10, Rolf Kreienberg11, Thomas Müller12, Thorsten Kühn13, Christopher Wolf14, Steffen Kahlert16, Stefan Paepke15, Michael Berghorn17, Mathias Muth18, Monika Baier18, Birgit Wackwitz18, Rüdiger Schulz-Wendtland19, Matthias W Beckmann1 and Michael P Lux1

Author Affiliations

1 University Breast Center, Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany

2 Departement of Gynecology and Obstetrics, Spital Rheinfelden, Switzerland

3 Breast Center, Klinikum Essen-Mitte, Essen, Germany

4 Department of Gynecology and Obstetrics, Essen University Hospital, Essen, Germany

5 Department of Gynecology and Obstetrics, Cologne University Hospital, Cologne, Germany

6 Kliniken der Stadt Köln Holweide, Cologne, Germany

7 Clinic for Gynecology and Obstetrics "Nathanstift" Klinikum Fürth, Fürth, Germany

8 Department of Gynecology and Obstetrics, Klinikum Harlaching, Munich, Germany

9 Department of Gynecology and Obstetrics, Sana-Klinikum Lichtenberg, Oskar-Ziethen-Krankenhaus, Berlin, Germany

10 Department of Gynecology and Obstetrics, Freiburg University Hospital, Freiburg, Germany

11 Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

12 Frauenklinik, Klinikum Hanau, Hanau, Germany

13 Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany

14 Medizinisches Zentrum Ulm, Ulm, Germany

15 Frauenklinik und Poliklinik der Technischen Universität München, Munich, Germany

16 Frauenklinik Grosshadern, Universitätsklinik der Ludwig-Maximilians-Universität, Munich, Germany

17 Frauenklinik, Allgemeines Krankenhaus Celle, Celle, Germany

18 Novartis Pharma GmbH, Nuremberg, Germany

19 Institute of Diagnostic Radiology, Erlangen University Hospital, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

For all author emails, please log on.

BMC Cancer 2014, 14:66  doi:10.1186/1471-2407-14-66

Published: 5 February 2014

Abstract

Background

The objective of this prospectively randomized phase II trial (Trial registration: EUCTR2004-004007-37-DE) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone (LET) or letrozole and zoledronic acid (LET + ZOL).

Methods

Patients were randomly assigned to receive either LET 2.5 mg/day (n = 79) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks (n = 89) for 6 months. Primary endpoint was clinical response rate as assessed by mammogram readings. The study was terminated prematurely due to insufficient recruitment. We report here on an exploratory analysis of this data.

Results

Central assessment of tumor sizes during the treatment period was available for 131 patients (66 LET, 65 LET + ZOL). Clinical responses (complete or partial) were seen in 54.5% (95% CI: 41.8-66.9) of the patients in the LET arm and 69.2% (95% CI: 56.6-80.1) of those in the LET + ZOL arm (P = 0.106). A multivariate model showed an OR of 1.72 (95% CI: 0.83-3.59) for the experimental arm.

Conclusion

No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET. However a trend towards a better reponse in the LET + ZOL arm could be observed. This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy, and it may support the evidence for a direct antitumor action of zoledronic acid.

Keywords:
Zoledronic acid; Neoadjuvant treatment; Breast cancer; Letrozole; Aromatase inhibitors; Bisphosphonates