title: Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide.
abstract: OBJECTIVE
  In a previous phase I-II study, the safety profile and anti-tumor efficacy of pre-targeting locoregional radioimmunotherapy (LR-RIT), based on the ''3 step'' method, was assessed in 24 high-grade glioma patients. The encouraging results in terms of low toxicity and objective response rate (25%) prompted us to continue our study.
  
  
  METHODS
  An analysis of 73 patients with hystologically confirmed glioblastoma multiforme (GBM), treated with the ''3 step'' (90)Y-biotin based LR-RIT, is herein reported. All patients had a catheter implanted at 2(nd) surgery and underwent at least 2 cycles of LR-RIT (range 2-7) with 2 months interval. Thirty-five out of 73 patients were also treated with Temozolomide (TMZ). Two cycles of TMZ (200 mg/m(2)/day, for 5/28 days) were administered in between each course of LR-RIT. Overall survival (OS) and progression free survival (PFS) were retrospectively calculated.
  
  
  RESULTS
  Stabilization of disease was achieved in 75% of patients, while 25% progressed. In the 38 patients treated with LR-RIT alone, median OS and PFS were respectively 17.5 months (95%CI=[17-20]) and 5 months (95%CI=[4-8]), while in the 35 treated with the combined treatment (LR-RIT+TMZ) respective values were 25 months (95%CI=[23-30]) and 10 months (95%CI=[9-18] (p<0.01). The addition of TMZ to LR-RIT did not increase neurological toxicity, and no major hematological toxicity was observed.
  
  
  CONCLUSIONS
  These results confirm the safety and the efficacy of (90)Y LR-RIT in recurrent GBM patients; the addition of TMZ significantly improved the overall outcomes; a further controlled prospective, randomized study is fully justified.
authors.affiliation: Division of Nuclear Medicine, IEO, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bartolomei
authors.forename: C
authors.initials: C
authors.lastname: Mazzetta
authors.forename: D
authors.initials: D
authors.lastname: Handkiewicz-Junak
authors.forename: L
authors.initials: L
authors.lastname: Bodei
authors.forename: P
authors.initials: P
authors.lastname: Rocca
authors.forename: C
authors.initials: C
authors.lastname: Grana
authors.forename: G
authors.initials: G
authors.lastname: Maira
authors.forename: C
authors.initials: C
authors.lastname: Sturiale
authors.forename: G
authors.initials: G
authors.lastname: Villa
authors.forename: G
authors.initials: G
authors.lastname: Paganelli
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001710:Biotin / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D001710:Biotin; D003606:Dacarbazine; D000077204:Temozolomide