Zoledronic acid in patients with stage IIIA/B NSCLC: results of a randomized, phase III study.
BACKGROUND
Bone metastases are common in patients with advanced non-small-cell lung cancer (NSCLC) and can have devastating consequences. Preventing or delaying bone metastases may improve outcomes.


METHODS
This study evaluated whether zoledronic acid (ZOL) delayed disease progression or recurrence in patients with controlled stage IIIA/B NSCLC after first-line therapy. Patients received vitamin D and calcium supplementation and were randomized to i.v. ZOL (every 3-4 weeks) or no treatment (control). The primary end point was progression-free survival (PFS).


RESULTS
No significant intergroup differences were observed in PFS or overall survival (OS). Median PFS was 9.0 months with ZOL versus 11.3 months for control. Fifteen ZOL-treated (6.6%) and 19 control patients (9.0%) developed bone metastases. Estimated 1-year OS was 81.8% for each group. ZOL safety profile was consistent with previous clinical data, but with higher discontinuations versus control. Fifteen ZOL-treated (6.6%) and five control patients (2.3%) had renal adverse events. Two cases of osteonecrosis of the jaw were reported.


CONCLUSIONS
ZOL did not significantly affect PFS or OS in stage IIIA/B NSCLC patients with controlled disease, with a trend toward worsening PFS in the longer-term follow-up. Few patients experienced bone metastases, possibly limiting the potential ZOL impact on disease course.
Department of Clinical and Biological Sciences, University of Turin, Torino, Italy. Electronic address: giorgio.scagliotti@unito.it.
G V
GV
Scagliotti
Department of Oncology, Hygeia Hospital, Athens, Greece.
P
P
Kosmidis
Pulmonary Oncological Unit, San Camillo Hospital, Rome, Italy.
F
F
de Marinis
Department of Pulmonary Diseases, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
A J M
AJM
Schreurs
Department of Pulmonology, Mátrai Gyógyintézet, Mátraháza, Hungary.
I
I
Albert
Department of Medical Oncology, Lung Clinic Merheim, Cologne, Germany.
W
W
Engel-Riedel
Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
D
D
Schallier
Department of Medical Oncology, Mariano Santo Hospital, Cosenza, Italy.
S
S
Barbera
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
H-P
HP
Kuo
Novartis Pharmaceuticals Corporation, East Hanover, USA.
V
V
Sallo
Novartis Pharmaceuticals Corporation, East Hanover, USA.
J R
JR
Perez
Department of Surgery, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
C
C
Manegold
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D002118:Calcium / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D019587:Dietary Supplements; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014807:Vitamin D / Q000008:administration & dosage; D055815:Young Adult; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D014807:Vitamin D; D000077211:Zoledronic Acid; D002118:Calcium