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 tumorassociated 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/μl (range, 1.4–3.5K/μl) occurred at a median of 4.5 weeks and the median platelet nadir of 41K/μl (range, 20–78K/μl) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4 14 patients (28%) at doses < 100 mCi whereas at doses ⩾ 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.