title: A phase I/II study of the intralesional injection of ricin-monoclonal antibody conjugates in patients with hepatic metastases.
abstract: A phase I/II study of the intralesional administration of ricin-labelled monoclonal antibodies was conducted in patients with hepatic metastases of gastrointestinal origin. The anti-carcinoembryonic antigen (CEA) antibody I-1 was conjugated to blocked ricin via a disulphide bridge. After a test dose of antibody, patients were injected with ricin-antibody conjugates under computed tomography (CT) guidance on two occasions 1 week apart. Patients with stable or responding disease would receive a third course. The dose of ricin relative to surface area was increased in a predefined manner in cohorts of 3 patients. A total of 27 patients with hepatic metastases were entered into this study. All patients had metastatic colorectal cancer (26 patients) or adenocarcinoma of unknown primary with elevated CEA levels (1 patient). The presence of malignancy was documented cytologically in 9 of 11 patients tested. Minor responses were seen in 7 patients. However, no major objective responses or changes in the growth rate of injected lesions were observed. Toxicity was generally mild, the most common being hepatic capsular pain 24-48 h after each injection. 6 patients experienced rigors. One patient had anaphylaxis. Human anti-mouse and anti-ricin antibody responses were observed. Although substantial amounts of ricin conjugated to monoclonal antibodies were delivered into single lesions, this therapeutic approach was unsuccessful. Future studies of ricin-labelled antibodies should incorporate the systemic administration of immunoconjugates.
authors.affiliation: Medical Oncology Department, Heidelberg Repatriation Hospital, Victoria, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: G
authors.initials: G
authors.lastname: Pietersz
authors.forename: B
authors.initials: B
authors.lastname: Toohey
authors.forename: J
authors.initials: J
authors.lastname: Laird
authors.forename: R
authors.initials: R
authors.lastname: Huggins
authors.forename: A S
authors.initials: AS
authors.lastname: Zimet
authors.forename: O
authors.initials: O
authors.lastname: Hennessy
authors.forename: A
authors.initials: A
authors.lastname: McKenzie
authors.forename: I F
authors.initials: IF
authors.lastname: McKenzie
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000628:therapy; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012276:Ricin / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D012276:Ricin