title: Interim analysis of toxicity and response in phase 1 trial of systemic targeted alpha therapy for metastatic melanoma.
abstract: OBJECTIVE
  The aim is to assess toxicity and response of systemic alpha therapy for metastatic melanoma.
  
  
  METHODS
  This is an open-labelled Phase 1 dose escalation study to establish the effective dose of the alpha-immunoconjugate (213)Bi-cDTPA-9.2.27 mAb (AIC). Tools used to investigate the effects were physical examination; imaging of tumors; pathology; GFR; CT and changes in tumor marker. Responses were assessed using RECIST criteria.
  
  
  CONCLUSIONS
  Twenty-two patients with stage IV melanoma/in-transit metastasis were treated with activities of 55-947 MBq. Using RECIST criteria 50% showed stable disease and 14% showed partial response. One patient (6%) showed near complete response and was retreated because of an excellent response to the initial treatment. Another patient showed response in his tumor on mandible and reduction in lung lesions. Overall 30% showed progressive disease. The tumor marker melanoma inhibitory activity protein (MIA) showed reductions over eight weeks in most of the patients. The disparity of dose with responders is discussed. No toxicity was observed over the range of administered activities.
  
  
  CONCLUSIONS
  Observation of responses without any toxicity indicates that targeted alpha therapy has the potential to be a safe and effective therapeutic approach for metastatic melanoma.
authors.affiliation: CERO, St. George Hospital, Kogarah, Australia.
authors.forename: Chand
authors.initials: C
authors.lastname: Raja
authors.forename: Peter
authors.initials: P
authors.lastname: Graham
authors.forename: Syed M
authors.initials: SM
authors.lastname: Abbas Rizvi
authors.forename: Emma
authors.initials: E
authors.lastname: Song
authors.forename: Helen
authors.initials: H
authors.lastname: Goldsmith
authors.forename: John
authors.initials: J
authors.lastname: Thompson
authors.forename: Anja
authors.initials: A
authors.lastname: Bosserhoff
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.forename: Christos
authors.initials: C
authors.lastname: Apostolidis
authors.forename: John
authors.initials: J
authors.lastname: Kearsley
authors.forename: Ralph
authors.initials: R
authors.lastname: Reisfeld
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Allen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D004369:Pentetic Acid / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C528533:213Bi-cDTPA-9.2.27 monoclonal antibody; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004369:Pentetic Acid