title: Impact of zoledronic acid on renal function in patients with cancer: Clinical significance and development of a predictive model.
abstract: Zoledronic acid is a potent bisphosphonate licensed for the treatment of myeloma and bone metastases from solid tumors. Renal deterioration is the most significant toxicity associated with zoledronic acid. We attempted to define the incidence and clinical significance of renal deterioration in patients receiving zoledronic acid and to develop a risk-factor profile for this treatment sequela. This study is a retrospective analysis of all patients who received zoledronic acid at Fox Chase Cancer Center, Philadelphia, Pa, between 1/10/02 and 1/30/04. Data recorded included patient demographics, tumor characteristics, comorbid illnesses, concomitant medications, cancer therapy, number of zoledronic acid doses administered, and serial creatinine measurements. In total, 3,115 evaluable doses of zoledronic acid were administered to 446 patients (median, 4 doses; mean, 6.98 doses; range, 1-28 doses) at a dose of 4 mg over 15 minutes every 3-4 weeks. Of these 446 patients, 42 experienced renal deterioration (median rise in creatinine level, 1.0 mg/dL; range, 0.5-4.4 mg/dL), requiring discontinuation of zoledronic acid therapy in 8 cases. No patient required dialysis and no patient died as a result of zoledronic acid-induced renal dysfunction. On multivariable analysis, predictive factors for the development of renal deterioration were patient age, a diagnosis of myeloma or renal cell cancer, cumulative number of doses, concomitant therapy with a nonsteroidal anti-inflammatory drug, and current or prior therapy with cisplatin. Using these factors, we constructed a predictive model with an area under the receiver operating characteristic curve of 0.75. The incidence of clinically significant renal deterioration in patients treated with zoledronic acid is low.We present a predictive model for decision support when estimating this risk.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Raymond S
authors.initials: RS
authors.lastname: McDermott
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Kloth
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D004164:Diphosphonates / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D015233:Models, Statistical; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D012189:Retrospective Studies; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid