title: A Phase I trial of samarium-153-lexidronam complex for treatment of clinically nonmetastatic high-risk prostate cancer: first report of a completed study.
abstract: OBJECTIVE
  We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP (153Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer.
  
  
  METHODS
  High-risk M0 prostate cancer patients (prostate-specific antigen>20 ng/mL, Gleason score>7, or>T3) were eligible for this prospective trial of dose-escalated radioactive 153Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered 153Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD=70.2 Gy). The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria.
  
  
  RESULTS
  Twenty-nine patients enrolled (median prostate-specific antigen=8.2 ng/mL, 27/29 (93%) T stage≥T2b, 24/29 (83%) had Gleason>7) and received 153Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0 mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7%) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects.
  
  
  CONCLUSIONS
  Our trial demonstrates that 2 mCi/kg 153Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.
authors.affiliation: Department Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA 95817, USA. richard.valicenti@ucdmc.ucdavis.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Valicenti
authors.forename: Edouard
authors.initials: E
authors.lastname: Trabulsi
authors.forename: Charles
authors.initials: C
authors.lastname: Intenzo
authors.forename: Jorosali
authors.initials: J
authors.lastname: Lavarino
authors.forename: Yihuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Inna
authors.initials: I
authors.lastname: Chervoneva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy / Q000379:methods; D005240:Feasibility Studies; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011879:Radiotherapy Dosage; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C061972:samarium Sm-153 lexidronam; D017430:Prostate-Specific Antigen