title: Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I(131) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma.
abstract: BACKGROUND
  Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy) provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I(131) in pancreatic cancer (ISRCTN 16857581).
  
  
  METHODS
  Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death.
  
  
  RESULTS
  Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33%) patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3).The overall response rate was 6% (1/18). Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months), with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79). One patient was still alive at the time of this analysis.
  
  
  CONCLUSIONS
  Dose limiting toxicity for KAb201 with I(131) by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.
authors.affiliation: Division of Surgery and Oncology, University of Liverpool, Liverpool, UK. asmasul@liv.ac.uk
authors.forename: Asma
authors.initials: A
authors.lastname: Sultana
authors.forename: Susannah
authors.initials: S
authors.lastname: Shore
authors.forename: Michael Gt
authors.initials: MG
authors.lastname: Raraty
authors.forename: Sobhan
authors.initials: S
authors.lastname: Vinjamuri
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Evans
authors.forename: Catrin Tudur
authors.initials: CT
authors.lastname: Smith
authors.forename: Steven
authors.initials: S
authors.lastname: Lane
authors.forename: Seema
authors.initials: S
authors.lastname: Chauhan
authors.forename: Lorraine
authors.initials: L
authors.lastname: Bosonnet
authors.forename: Conall
authors.initials: C
authors.lastname: Garvey
authors.forename: Robert
authors.initials: R
authors.lastname: Sutton
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000276:immunology; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D011859:Radiography; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes