title: Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer.
abstract: BACKGROUND
  Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of 153Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy.
  
  
  METHODS
  Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was <or=10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with 153Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after 153Sm-EDTMP (14 patients, group B) or within 1 month after 153Sm-EDTMP (16 patients, group C).
  
  
  RESULTS
  Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either 153Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both 153Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by 153Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of 153Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008).
  
  
  CONCLUSIONS
  The results of this study confirm that 153Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies.
authors.affiliation: Division of Medical Oncology, Department of Oncology, University Hospital, Pisa, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pastina
authors.forename: Dario
authors.initials: D
authors.lastname: Genovesi
authors.forename: Claudia
authors.initials: C
authors.lastname: Cianci
authors.forename: Serena
authors.initials: S
authors.lastname: Chiacchio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Orlandini
authors.forename: Mariano
authors.initials: M
authors.lastname: Grosso
authors.forename: Abedallatif
authors.initials: A
authors.lastname: Alsharif
authors.forename: Aldo
authors.initials: A
authors.lastname: Chioni
authors.forename: Samantha
authors.initials: S
authors.lastname: Di Donato
authors.forename: Francesco
authors.initials: F
authors.lastname: Francesca
authors.forename: Cesare
authors.initials: C
authors.lastname: Selli
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Giuliano
authors.initials: G
authors.lastname: Mariani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000150:complications / Q000556:secondary* / Q000628:therapy*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010166:Palliative Care / Q000379:methods; D011471:Prostatic Neoplasms / Q000150:complications / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant / Q000379:methods; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D004338:Drug Combinations; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C061972:samarium Sm-153 lexidronam