title: Safety and antitumor efficacy of (153)Sm-EDTMP and docetaxel administered sequentially to patients with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Bone metastases are responsible for most of the morbidity associated with metastatic castration-resistant prostate cancer (mCRPC). Bone-seeking radiopharmaceuticals have been approved for palliation of painful skeletal metastases, but their clinical use is limited by concerns of toxicities both when administered alone and especially when combined with chemotherapy agents.
  
  
  OBJECTIVE
  We investigated whether docetaxel administered to mCRPC patients after treatment with samarium-153-labeled ethylene-diamine-tetra-methylene-phosphonic acid (Sm-EDTMP) has increased toxicity and/or reduced antitumor efficacy.
  
  
  METHODS
  Thirty mCRPC patients with skeletal metastases were enrolled. Patients received standard therapy with docetaxel (75 mg/m intravenously every 21 days for at least six cycles) on average 6 weeks after Sm-EDTMP (37 MBq/kg). Patients were monitored for the presence of toxicities, and antitumor efficacy was assessed by changes in serum prostate-specific antigen levels. Besides standard descriptive statistical analysis, progression-free survival and overall survival were defined using the Kaplan-Meier method.
  
  
  RESULTS
  Over 80% of the patients showed favorable biochemical responses. Median time to progression was 9.1 months (mean 9.8, 95% confidence interval 7.8-9.9), and median overall survival was 19.9 months (mean 24.5, 95% confidence interval 16.9-22.8); five patients were still alive over 5 years after enrollment. No additional hematological toxicities were observed when docetaxel was administered after Sm-EDTMP other than those expected when administering the agent alone.
  
  
  CONCLUSIONS
  Prior administration of Sm-EDTMP does not cause additional toxicities for subsequent treatment with docetaxel and does not reduce the antitumor efficacy of the latter. This work justifies further investigations on the possible synergistic effects of combined strategies with the two agents.
authors.affiliation: aRegional Center of Nuclear Medicine dDivision of Urology, University of Pisa bDivision of Medical Oncology cDivision of Urology, University Hospital of Pisa, Pisa eDepartment of Nuclear Medicine & PET/CT Centre, 'Santa Maria della Misericordia' Hospital, Rovigo, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Borsò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pastina
authors.forename: Alice
authors.initials: A
authors.lastname: Lorenzoni
authors.forename: Claudia
authors.initials: C
authors.lastname: Cianci
authors.forename: Francesca
authors.initials: F
authors.lastname: Federici
authors.forename: Sara
authors.initials: S
authors.lastname: Mazzarri
authors.forename: Cinzia
authors.initials: C
authors.lastname: Orlandini
authors.forename: Francesco
authors.initials: F
authors.lastname: Francesca
authors.forename: Cesare
authors.initials: C
authors.lastname: Selli
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Giuliano
authors.initials: G
authors.lastname: Mariani
mesh_terms: D000368:Aged; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D012449:Safety; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D043823:Taxoids; D000077143:Docetaxel; C061972:samarium Sm-153 lexidronam