title: Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125.
abstract: Refractory epithelial ovarian cancer is generally confined to the peritoneal cavity and is thus amenable to intraperitoneal (ip) therapy. Radiolabeled monoclonal antibodies raised to tumor-associated antigens offer the promise of selective tumor irradiation while reducing toxicity to normal tissues. We have conducted a phase I therapeutic trial to examine the feasibility of ip radioimmunotherapy utilizing escalating doses of 131I-labeled OC125 F(ab')2. Twenty-nine patients were each treated with a single dose of radiolabeled antibody. Twenty-eight patients were evaluable for dose-related toxicity. The toxicities most frequently observed were hematologic and gastrointestinal. Hematologic toxicity was noted in 5/14 (36%) patients receiving 18-87 mCi and in 12/14 (71%) receiving 100-144 mCi (P = 0.018). The median white blood cell nadir of 2-3K/microliters (range, 1.4-3.5K/microliters occurred at a median of 4.5 weeks and the median platelet nadir of 41K/microliters (range, 20-78K/microliters) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4/14 patients (28%) at doses less than 100 mCi whereas at doses greater than or equal to 100 mCi, 11/14 (79%) patients developed nausea, vomiting, or chronic ileus (P = 0.021). This toxicity occurred most frequently in patients with protracted urinary 131I excretion. We conclude that 131I-labeled OC125 can be safely administered ip. Hematologic and gastrointestinal toxicity is predictable and related to the dose and rate of clearance of isotope.
authors.affiliation: Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: M G
authors.initials: MG
authors.lastname: Muto
authors.forename: N J
authors.initials: NJ
authors.lastname: Finkler
authors.forename: A I
authors.initials: AI
authors.lastname: Kassis
authors.forename: A E
authors.initials: AE
authors.lastname: Howes
authors.forename: L L
authors.initials: LL
authors.lastname: Anderson
authors.forename: C C
authors.initials: CC
authors.lastname: Lau
authors.forename: V R
authors.initials: VR
authors.lastname: Zurawski
authors.forename: K
authors.initials: K
authors.lastname: Weadock
authors.forename: S S
authors.initials: SS
authors.lastname: Tumeh
authors.forename: P
authors.initials: P
authors.lastname: Lavin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D002277:Carcinoma / Q000276:immunology / Q000532:radiotherapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000506:poisoning; D051379:Mice / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes