Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial--the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group.
OBJECTIVE
To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer.


METHODS
Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE.


RESULTS
Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P =.127 and P =.023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P =.023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P =.017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting.


CONCLUSIONS
Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.
Rosen
Lee S
LS
Cancer Institute Medical Group, 11818 Wilshire Blvd, Suite 200, Los Angeles, CA 90025, USA. lrosen@cimg.org.
Gordon
David
D
Tchekmedyian
Simon
S
Yanagihara
Ronald
R
Hirsh
Vera
V
Krzakowski
M
M
Pawlicki
M
M
de Souza
Paul
P
Zheng
Ming
M
Urbanowitz
Gladys
G
Reitsma
Dirk
D
Seaman
John J
JJ
D001859:Bone Neoplasms / Q000556:secondary*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology; D010919:Placebos; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid