{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:15:33Z","timestamp":1791778533213,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,8,5]],"date-time":"2008-08-05T00:00:00Z","timestamp":1217894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND.<\/jats:title>\n                    <jats:p>Bisphosphonates (BPs) are effective in the prevention and treatment of skeletal\u2010related 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS.<\/jats:title>\n                    <jats:p>The authors conducted a prospective, multicenter, open\u2010label, phase 3, randomized trial comparing the administration of zoledronic acid versus simple observation in patients with AM. One\u2010hundred sixty\u2010three 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\u2010minute, intravenous infusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS.<\/jats:title>\n                    <jats:p>\n                      After a median follow\u2010up of 64.7 person\u2010months, 44.4% of patients in the zoledronic acid group and 45.1% of the control group progressed to \u2018symptomatic\u2019 myeloma requiring chemotherapy (\n                      <jats:italic>P<\/jats:italic>\n                      = .9307). The median time to progression was 67 months and 59 months for the treatment and control groups, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      = .8312). At progression, SREs were significantly lower in the zoledronic acid\u2010treated group (55.5%) than in the control group (78.3%;\n                      <jats:italic>P<\/jats:italic>\n                      = .041), whereas anemia, renal failure, and extramedullary disease were not statistically different. More frequent adverse events observed in the zoledronic acid\u2010treated group were asymptomatic hypocalcemia and fever. One patient developed reversible osteonecrosis of the jaw. No renal failure caused by zoledronic acid was reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS.<\/jats:title>\n                    <jats:p>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. Cancer 2008. \u00a9 2008 American Cancer Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.23783","type":"journal-article","created":{"date-parts":[[2008,8,5]],"date-time":"2008-08-05T12:47:18Z","timestamp":1217940438000},"page":"1588-1595","source":"Crossref","is-referenced-by-count":160,"title":["A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma"],"prefix":"10.1002","volume":"113","author":[{"given":"Pellegrino","family":"Musto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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