title: Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma.
abstract: BACKGROUND
  The objective of this study was to assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to renal cell carcinoma (RCC).
  
  
  METHODS
  A retrospective subset analysis of patients with RCC enrolled in a multicenter, randomized, placebo-controlled study of zoledronic acid was performed. Patients were randomized to receive zoledronic acid (4 or 8 mg as a 15-minute infusion) or placebo with concomitant antineoplastic therapy every 3 weeks for 9 months. The primary efficacy analysis was the proportion of patients with one or more skeletal-related events (SREs), which were defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate (events per year), disease progression, and multiple event analysis.
  
  
  RESULTS
  In this subset of 74 patients with RCC, zoledronic acid (4 mg) was found to significantly reduce the proportion of patients with an SRE (37% vs. 74% for placebo; P = 0.015). Similarly, zoledronic acid significantly reduced the mean skeletal morbidity rate (2.68 vs. 3.38 for placebo; P = 0.014) and extended the time to the first event (median not reached vs. 72 days for placebo; P = 0.006). A multiple event analysis demonstrated that the risk of developing an SRE was reduced by 61% compared with placebo (hazard ratio of 0.394; P = 0.008). The median time to progression of bone lesions was significantly longer for patients who were treated with zoledronic acid (P = 0.014 vs. placebo). Zoledronic acid appeared to be well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and emesis.
  
  
  CONCLUSIONS
  Zoledronic acid (4 mg as a 15-minute infusion) demonstrated significant clinical benefit in patients with bone metastases from RCC, suggesting that further investigation of zoledronic acid in this patient population is warranted.
authors.affiliation: Department of Medicine, Milton S. Hershey Medical Center, PO Box 850 H-46, Hershey, PA 17033, USA. alipton@psu.edu
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: John
authors.initials: J
authors.lastname: Seaman
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000556:secondary*; D004164:Diphosphonates / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012189:Retrospective Studies; D013117:Spinal Cord Compression / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid