title: Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study.
abstract: Malignant bone disease can cause significant morbidity. Monthly zoledronic acid (ZOL) reduces skeletal complications; however, limited data are available regarding long-term safety. We aimed to assess efficacy and safety of ZOL beyond 1 year of treatment. We prospectively evaluated 73 patients; breast cancer (n = 29), castrate-resistant prostate cancer (n = 13), multiple myeloma (n = 31) from 2006 to 2008 in 19 cancer centres. All patients were diagnosed with bone disease and had completed 1-2 years of monthly ZOL (4 mg) and received a further 1-2 years of therapy following contemporary guidelines for managing risks of osteonecrosis of the jaw (ONJ) and renal toxicity. Overall rates of skeletal-related events (SREs), renal impairment and ONJ were assessed. Over the additional 1 year of treatment, only 5.5% (n = 4) of patients developed a new SRE. The overall Kaplan-Meier estimate for SRE incidence after 48 weeks on study was 6.75% (95 CI: 2.5-17.3). Although 51% of patients reported serious adverse events, only two cases were suspected as ZOL related. No patients had confirmed ONJ. The observed incidence of new renal impairment was 11% (none due to ZOL). Our study confirms the benefit over risk of continuing monthly ZOL for at least 2 years in patients with advanced cancer involving bone.
authors.affiliation: Launceston General Hospital, Launceston, TAS., Australia.|Menzies Research Institute, Faculty of Health Sciences, University of Tasmania, Launceston, TAS., Australia.
authors.forename: A A
authors.identifier: http://orcid.org/0000-0002-2399-3311
authors.initials: AA
authors.lastname: Khalafallah
authors.affiliation: Haematology & Oncology Clinics of Australia - Southport, Southport, Qld, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Slancar
authors.affiliation: John Fawkner Cancer Trial Centre, Coburg, Vic., Australia.
authors.forename: W
authors.initials: W
authors.lastname: Cosolo
authors.affiliation: Griffith University, The Tweed Hospital, Tweed Heads, NSW, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Abdi
authors.affiliation: Redcliffe Hospital, Redcliffe, Qld, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Chern
authors.affiliation: Novartis Pharmaceuticals Australia Pty Ltd, North Ryde, NSW, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Woodfield
authors.affiliation: Manly Hospital, Manly, NSW, Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Copeman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001847:Bone Diseases / Q000188:drug therapy*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011446:Prospective Studies; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: bone metastasis; long-term safety; osteonecrosis of the jaw; renal impairment; zoledronic acid