title: A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma.
abstract: BACKGROUND
  Bisphosphonates (BPs) are effective in the prevention and treatment of skeletal-related events (SREs) in patients with symptomatic myeloma who are receiving chemotherapy. Recent data also suggest a possible antineoplastic activity of BPs. Few studies published to date have explored the role of BPs in patients with untreated, asymptomatic myeloma (AM). No data are available on the efficacy of zoledronic acid in these patients.
  
  
  METHODS
  The authors conducted a prospective, multicenter, open-label, phase 3, randomized trial comparing the administration of zoledronic acid versus simple observation in patients with AM. One-hundred sixty-three patients were enrolled and randomized (1:1) to receive zoledronic acid (n = 81 patients) or not to receive zoledronic acid (n = 82 patients) for 1 year at a dose of 4 mg monthly as a single, 15-minute, intravenous infusion.
  
  
  RESULTS
  After a median follow-up of 64.7 person-months, 44.4% of patients in the zoledronic acid group and 45.1% of the control group progressed to 'symptomatic' myeloma requiring chemotherapy (P = .9307). The median time to progression was 67 months and 59 months for the treatment and control groups, respectively (P = .8312). At progression, SREs were significantly lower in the zoledronic acid-treated group (55.5%) than in the control group (78.3%; P = .041), whereas anemia, renal failure, and extramedullary disease were not statistically different. More frequent adverse events observed in the zoledronic acid-treated group were asymptomatic hypocalcemia and fever. One patient developed reversible osteonecrosis of the jaw. No renal failure caused by zoledronic acid was reported.
  
  
  CONCLUSIONS
  The monthly use of zoledronic acid for 1 year in patients with AM reduced the development of SREs at progression but did not influence the natural history of the disease.
authors.affiliation: Unit of Hematology and Stem Cell Transplantation, IRCCS-Oncology Referral Center of Basilicata, Rionero in Vulture (Pz), Italy. p.musto@crob.it
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Tommasina
authors.initials: T
authors.lastname: Guglielmelli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Velia
authors.initials: V
authors.lastname: Bongarzoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Andriani
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.forename: Enrico
authors.initials: E
authors.lastname: Balleari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pietrantuono
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001847:Bone Diseases / Q000517:prevention & control*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D016019:Survival Analysis; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid