title: Results of a multicenter open-label randomized trial evaluating infusion duration of zoledronic acid in multiple myeloma patients (the ZMAX trial).
abstract: Zoledronic acid, an intravenous (IV) bisphosphonate, is a standard treatment for multiple myeloma (MM) but may exacerbate preexisting renal dysfunction. The incidence of zoledronic acid-induced renal dysfunction may correlate with infusion duration. In this randomized, multicenter, open-label study, 176 patients with MM, at least one bone lesion, and stable renal function with a serum creatinine (SCr) level < 3 mg/dL received zoledronic acid 4 mg (in 250 mL) as a 15- or 30-minute IV infusion every 3-4 weeks. At month 12, 20% (17 patients) in the 15-minute and 16% (13 patients) in the 30-minute arm experienced a clinically relevant but nonsignificant SCr-level increase (P = 0.44). By 24 months, the proportion of patients with a clinically relevant SCr-level increase was similar between arms (15-minute 28% [24 patients] vs 30-minute 27% [23 patients], P = 0.9014). Median zoledronic acid end-of-infusion concentrations were higher with the shorter infusion (15-minute 249 ng/mL vs 30-minute 172 ng/mL), and prolonging the infusion beyond 15 minutes did not influence adverse events related to zoledronic acid. For patients with MM, the safety profile of IV zoledronic acid is similar between those receiving a 15- or 30-minute infusion; therefore, determining the appropriate infusion duration of zoledronic acid should be based on individual patient considerations.
authors.affiliation: Institute for Myeloma & Bone Cancer Research, West Hollywood, California 90069, USA. jberenson@imbcr.org
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.forename: Timothy
authors.initials: T
authors.lastname: Lopez
authors.forename: Ghulam M
authors.initials: GM
authors.lastname: Warsi
authors.forename: Eliza
authors.initials: E
authors.lastname: Argonza-Aviles
authors.forename: Simone
authors.initials: S
authors.lastname: Lake
authors.forename: Solveig G
authors.initials: SG
authors.lastname: Ericson
authors.forename: Robert
authors.initials: R
authors.lastname: Collins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid