Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial.
BACKGROUND
The goal of the current study was to compare the long-term (25-month) safety and efficacy of zoledronic acid with pamidronate in patients with bone lesions secondary to advanced breast carcinoma or multiple myeloma.


METHODS
Patients (n = 1648) were randomized to receive 4 mg or 8 mg (reduced to 4 mg) zoledronic acid as a 15-minute infusion or to receive 90 mg pamidronate as a 2-hour infusion every 3-4 weeks for 24 months. The primary endpoint was the proportion of patients with at least 1 skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate, and multiple-event analysis. Hypercalcemia of malignancy (HCM) was included as an SRE in some secondary analyses.


RESULTS
After 25 months of follow-up, zoledronic acid reduced the overall proportion of patients with an SRE and reduced the skeletal morbidity rate similar to pamidronate. Compared with pamidronate, zoledronic acid (4 mg) reduced the overall risk of developing skeletal complications (including HCM) by an additional 16% (P = 0.030). In patients with breast carcinoma, zoledronic acid (4 mg) was significantly more effective than pamidronate, reducing the risk of SREs by an additional 20% (P = 0.025) compared with pamidronate and by an additional 30% in patients receiving hormonal therapy (P = 0.009). Zoledronic acid (4 mg) and pamidronate were tolerated equally well. The most common adverse events included bone pain, nausea, and fatigue.


CONCLUSIONS
Long-term follow-up data confirm that zoledronic acid was more effective than pamidronate in reducing the risk of skeletal complications in patients with bone metastases from breast carcinoma and was of similar efficacy in patients with multiple myeloma.
Rosen
Lee S
LS
Developmental Therapeutics, Cancer Institute Medical Group, Santa Monica, California 90095, USA. RosenL@jwci.org
Gordon
David
D
Kaminski
Mary
M
Howell
Anthony
A
Belch
Andrew
A
Mackey
John
J
Apffelstaedt
Justus
J
Hussein
Mohamad A
MA
Coleman
Robert E
RE
Reitsma
Dirk J
DJ
Chen
Bee-Lian
BL
Seaman
John J
JJ
D001847:Bone Diseases / Q000188:drug therapy*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000150:complications*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications*; D000077268:Pamidronate; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate