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

BMC Cancer. 2009 Feb 25:9:66. doi: 10.1186/1471-2407-9-66.

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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnostic imaging*
  • Adenocarcinoma / immunology
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Neoplasm / biosynthesis
  • Antibodies, Neoplasm / immunology
  • Carcinoembryonic Antigen / administration & dosage*
  • Carcinoembryonic Antigen / adverse effects
  • Carcinoembryonic Antigen / immunology
  • Humans
  • Immunotoxins / administration & dosage*
  • Immunotoxins / adverse effects
  • Immunotoxins / immunology
  • Immunotoxins / pharmacokinetics
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Iodine Radioisotopes / administration & dosage*
  • Iodine Radioisotopes / adverse effects
  • Iodine Radioisotopes / pharmacokinetics
  • Middle Aged
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / radiotherapy*
  • Radiography
  • Radioimmunotherapy / adverse effects
  • Radioimmunotherapy / methods*
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Carcinoembryonic Antigen
  • Immunotoxins
  • Iodine Radioisotopes

Associated data

  • ISRCTN/ISRCTN16857581