title: Radioimmunotherapy in advanced ovarian cancer: is there a role for pre-targeting with (90)Y-biotin?
abstract: OBJECTIVE
  Despite recent advances in the management of ovarian cancer, this tumor remains the leading cause of death among gynecologic malignancies. Moreover, advanced ovarian carcinoma has a poor prognosis, thus requiring new therapeutic modalities. Previous studies have indicated a survival advantage for ovarian cancer patients (pts) treated with radioimmunotherapy (RIT). Pre-targeting RIT, based on the avidin-biotin system, has been the objective of previous studies performed by our group.
  
  
  METHODS
  In the present study, the therapeutic efficacy and toxicity of RIT in 38 advanced ovarian cancer patients have been retrospectively evaluated. RIT was performed according to the following three-step protocol: biotinylated monoclonal antibodies (MoAb) and avidin were intraperitoneally (ip) injected (1st and 2nd step), and 12-18 h later (90)Y-labeled biotin either iv or ip was injected as 3rd step. Sixteen out of 38 patients were treated by intraperitoneal injection only, whereas other 22 pts received the combined treatment (ip + iv); the dose range was 10-100 mCi of (90)Y-biotin.
  
  
  RESULTS
  Both of the two therapy regimens were well tolerated; no acute side effects were observed. Two patients (5%) showed temporary hematological grade III-IV toxicity. As regards to the therapeutic efficacy, in the ip group we observed 6% of objective tumor reduction, stabilization in 31% of pts, and progression in 50%. In the group of combined treatment, 9% of patients achieved objective responses, 32% showed stable disease, and 41% had a progression.
  
  
  CONCLUSIONS
  These data show the excellent tolerability (maximum tolerated dose (MTD) has not been determined yet) and the potential therapeutic role of RIT in advanced ovarian cancer. Patients with minimal residual disease would probably take the best advantages of RIT with (90)Y-biotin (electrons). These data warrant further prospective studies.
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, Milano, Italy. direzione.mnu@ieo.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Grana
authors.forename: Mirco
authors.initials: M
authors.lastname: Bartolomei
authors.forename: Daria
authors.initials: D
authors.lastname: Handkiewicz
authors.forename: Paola
authors.initials: P
authors.lastname: Rocca
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.forename: Marco
authors.initials: M
authors.lastname: Chinol
authors.forename: Costantino
authors.initials: C
authors.lastname: Mangioni
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001710:Biotin / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D012189:Retrospective Studies; D016879:Salvage Therapy; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D015021:Yttrium Radioisotopes; D001710:Biotin