title: Safety analysis of repeated high doses of samarium-153 lexidronam in men with hormone-naive prostate cancer metastatic to bone.
abstract: OBJECTIVE
  The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (153Sm- EDTMP) were investigated in men with hormone-naive prostate cancer metastatic to bone.
  
  
  METHODS
  Within 30 days of initiating androgen deprivation, the first of 4 planned doses of 153Sm- EDTMP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received 153Sm-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses.
  
  
  RESULTS
  There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received 153Sm-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of 153Sm-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of 153Sm-EDTMP. There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities.
  
  
  CONCLUSIONS
  In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repeated doses of 153Sm-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses.
authors.affiliation: Medicine and Urology, University of Washington Medical Center, Division of Medical Oncology, Seattle, WA 98109, USA. thigano@u.washington.edu
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Donald P
authors.initials: DP
authors.lastname: Quick
authors.forename: David
authors.initials: D
authors.lastname: Bushnell
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology / Q000628:therapy; D009942:Organometallic Compounds / Q000008:administration & dosage*; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy; D012493:Samarium; D015996:Survival Rate
chemical_list: D018712:Analgesics, Non-Narcotic; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D012493:Samarium; C061972:samarium Sm-153 lexidronam