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


CONCLUSIONS
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.
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. peter.fasching@uk-erlangen.de.
Peter A
PA
Fasching
Sebastian M
SM
Jud
Maik
M
Hauschild
Sherko
S
Kümmel
Martin
M
Schütte
Matthias
M
Warm
Volker
V
Hanf
Dieter
D
Grab
Jutta
J
Krocker
Elmar
E
Stickeler
Rolf
R
Kreienberg
Thomas
T
Müller
Thorsten
T
Kühn
Christopher
C
Wolf
Steffen
S
Kahlert
Stefan
S
Paepke
Michael
M
Berghorn
Mathias
M
Muth
Monika
M
Baier
Birgit
B
Wackwitz
Rüdiger
R
Schulz-Wendtland
Matthias W
MW
Beckmann
Michael P
MP
Lux
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D004164:Diphosphonates / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009570:Nitriles / Q000008:administration & dosage*; D011446:Prospective Studies; D014230:Triazoles / Q000008:administration & dosage*; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole