title: Phase I/II study of low-dose intravenous OKT3 and subcutaneous interleukin-2 in metastatic cancer.
abstract: In a phase I/II study the safety, immunostimulatory and antitumor effects of a combined OKT3/interleukin 2 (IL-2) treatment was studied in 15 cancer patients who failed IL-2 treatment. OKT3 was given as a 2-h intravenous infusion. Doses of 50, 100, 200 and 400 micrograms OKT3 were studied. Within 24 h, subcutaneous IL-2 was started 5 days/week for 4 weeks, at a dose of 9-18 x 10(6) U daily. Maximum tolerated dose was 400 micrograms OKT3 with neurotoxicity as dose-limiting toxicity. Toxicity of subcutaneous IL-2 was acceptable. At the maximum tolerated dose, 9 patients with renal cell carcinoma with measurable disease were treated in a phase II setting. 8 patients were evaluable for response. 4 patients had stable disease and 4 had progressive disease. An increase of activated lymphocyte subpopulations could not be found, although OKT3 was detectable on lymphocytes in vivo. Only if laboratory studies shed light on methods of improving immunostimulating effects of OKT3 will further clinical studies be warranted.
authors.affiliation: Department of Medical Oncology, University Hospital, Groningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Buter
authors.forename: R A
authors.initials: RA
authors.lastname: Janssen
authors.forename: A
authors.initials: A
authors.lastname: Martens
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
authors.forename: L
authors.initials: L
authors.lastname: de Leij
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007376:Interleukin-2; D016853:Muromonab-CD3