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.
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.
Ledermann
J A
JA
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Begent
R H
RH
Massof
C
C
Kelly
A M
AM
Adam
T
T
Bagshawe
K D
KD
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003524:Cyclosporins / Q000009:adverse effects / Q000494:pharmacology*; D004067:Digestive System Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010976:Platelet Count / Q000187:drug effects / Q000528:radiation effects; D012004:Rectal Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D003524:Cyclosporins