A phase II study of G17DT in gastric carcinoma

Eur J Surg Oncol. 2004 Jun;30(5):536-43. doi: 10.1016/j.ejso.2004.03.009.

Abstract

Purpose: G17DT is a gastrin immunogen, raising antibodies that blockade gastrin-stimulated growth. The aim of the study was to characterise antibody response and assess safety and tolerability of G17DT given to patients with gastric cancer.

Experimental design: G17DT was administered to 52 patients with gastric adenocarcinoma at weeks 0, 2 and 6 by intramuscular injection at doses of 10, 100 and 250 microg. Antibody levels were measured by an ELISA assay. A radioligand displacement assay determined the ability of G17DT-immunised patients' sera to inhibit binding of 125IG17 to cholecystokinin (CCK)-2 receptors.

Results: By week 12 of the study, 6/12 evaluable stage I-III patients achieved an antibody response in the 10 microg group, 7/11 in the 100 microg group, and 11/12 in the 250 microg group. Stage IV patients dosed at 250 microg achieved a similar response rate to stage I-III patients dosed at 10 or 100 microg. G17DT was well tolerated in 47/52 patients. Two patients suffered significant adverse reactions including injection site pain and abscess. G17DT antibodies displaced iodinated gastrin from CCK-2 receptors, with the level of displacement correlating with antibody titre.

Conclusions: G17DT immunisation is a well-tolerated method of raising functional antibodies to 17 amino acid gastrin forms in patients with gastric carcinomas.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Formation / drug effects*
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Gastrins*
  • Humans
  • Immune Sera / drug effects
  • Immune Sera / immunology
  • Immunization, Secondary
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Receptor, Cholecystokinin B / drug effects
  • Receptor, Cholecystokinin B / immunology
  • Statistics as Topic
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Gastrins
  • Immune Sera
  • Receptor, Cholecystokinin B
  • gastrin immunogen