title: Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases.
abstract: OBJECTIVE
  (153)Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated.
  
  
  METHODS
  Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg (153)Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before (153)Sm-EDTMP treatment. Urine was collected 48 h after injection of (153)Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of (153)Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied.
  
  
  RESULTS
  The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 +/- 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 +/- 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with (153)Sm-EDTMP.
  
  
  CONCLUSIONS
  Zoledronic acid treatment does not influence (153)Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe.
authors.affiliation: Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. M.Lam@umcutrecht.nl
authors.forename: Marnix G E H
authors.initials: MG
authors.lastname: Lam
authors.forename: Amel
authors.initials: A
authors.lastname: Dahmane
authors.forename: Wil H M
authors.initials: WH
authors.lastname: Stevens
authors.forename: Peter P
authors.initials: PP
authors.lastname: van Rijk
authors.forename: John M H
authors.initials: JM
authors.lastname: de Klerk
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Zonnenberg
mesh_terms: D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012493:Samarium / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D012493:Samarium; D000077211:Zoledronic Acid; C061972:samarium Sm-153 lexidronam