title: Pilot study of targeted skeletal radiation therapy for bone-only metastatic breast cancer.
abstract: OBJECTIVE
  Bone-targeted radiation therapy is an attractive strategy for addressing bone disease with minimal systemic toxicity. This pilot study was designed to determine the safety and efficacy of (166)Holmium (Ho)-DOTMP for irradiating malignant cells and adjacent marrow in women with bone-only metastatic breast cancer.
  
  
  METHODS
  Subjects included 6 women aged < or = 65 years with breast cancer and bone-only metastases at M. D. Anderson Cancer Center. The activity of (166)Ho-DOTMP was calculated to deliver a therapeutic absorbed dose of 22 Gy (n = 3) or 28 Gy (n = 3) to the marrow. Treatment was followed by autologous stem cell transplantation to circumvent the anticipated myelosuppresion. Median follow-up time was 40 months.
  
  
  RESULTS
  All subjects showed prompt hematologic recovery. No patient experienced grade 3/4 acute toxicity aside from myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy. One patient developed myelodysplastic syndrome but was found to have had pre-existing trisomy 8. Two patients remained progression free without evidence of disease for more than 6 years. Five women experienced disease relapse (4 at extraosseous sites) and died of progressive disease. Median time to progression was 10.4 months.
  
  
  CONCLUSIONS
  The approach of bone-targeted radiation therapy with (166)Ho-DOTMP had an acceptable toxicity profile, and sustained complete response was obtained in 2 of 6 patients. We are conducting a phase II study to evaluate the efficacy of targeted skeletal radiation therapy for treating bone-only metastases.
authors: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. nueno@mdanderson.org
authors: Naoto T
authors: NT
authors: Ueno
authors: Jonas A
authors: JA
authors: de Souza
authors: Daniel
authors: D
authors: Booser
authors: Kazutaka
authors: K
authors: Nakayama
authors: John
authors: J
authors: Madewell
authors: Richard E
authors: RE
authors: Wendt
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: Donald
authors: D
authors: Podoloff
authors: Richard E
authors: RE
authors: Champlin
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy*; D001842:Bone and Bones / Q000187:drug effects / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000493:pharmacokinetics; D036102:Peripheral Blood Stem Cell Transplantation; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D009943:Organophosphorus Compounds; C082084:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid)