A phase-I study of repeated therapy with radiolabelled antibody to carcinoembryonic antigen using intermittent or continuous administration of cyclosporin A to suppress the immune response

Int J Cancer. 1991 Mar 12;47(5):659-64. doi: 10.1002/ijc.2910470505.

Abstract

The anti-mouse antibody response was examined in patients receiving repeated i.v. therapy with radiolabelled mouse monoclonal antibody (MAb) to carcinoembryonic antigen (CEA): 131I anti-CEA was given approximately every 2 weeks with cyclosporin A, to suppress the anti-mouse antibody response. Two schedules of cyclosporin A--intermittent therapy for 6 days with each course of anti-CEA and continuous therapy--were compared. Suppression of the immune response in the intermittent high-dose (3 patients) and continuous low-dose groups (4 patients) was equivalent, but the latter regimen was less toxic. Repeated therapy led to the formation of small amounts of anti-mouse antibody, but provided that cyclosporin A was continued it did not prevent further therapy or lead to an increase in the rate of clearance of anti-CEA from blood. Without cyclosporin A no more than 2 courses of antibody therapy could be given. Patients received up to 4 doses of 131I anti-CEA. The nadir platelet count was related to the half-life of 131I anti-CEA in blood. Thrombocytopenia limited the amount of 131I anti-CEA that could be given and determined the interval between treatments. Effective suppression of the anti-antibody response is possible and this study has determined that myelosuppression is the principal obstacle to repeated therapy with radiolabelled antibody.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Carcinoembryonic Antigen / immunology*
  • Colonic Neoplasms / drug therapy
  • Cyclosporins / adverse effects
  • Cyclosporins / pharmacology*
  • Digestive System Neoplasms / drug therapy*
  • Drug Administration Schedule
  • Drug Evaluation
  • Drug Synergism
  • Female
  • Humans
  • Immune Tolerance / drug effects*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Platelet Count / drug effects
  • Platelet Count / radiation effects
  • Rectal Neoplasms / drug therapy
  • Stomach Neoplasms / drug therapy

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Cyclosporins