Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer.

Abstract

From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient.

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

“…We have previously described extensively the pharmacokinetics, biodistribution and toxicity of iodine-1 31 and yttrium-90-labelled monoclonal antibodies for the treatment of ovarian cancer (Epenetos et al, 1987;Stewart et al, 1989Stewart et al, , 1990Maraveyas et al, 1993) (Stewart et al, 1990;Meares et al, 1990). …”

“…No obvious reduction in immunoreactivity was seen. The administered dose of radioactivity was measured in a SIEL isotope calibration chamber that had been calibrated with an yttrium-90 source (Stewart et al, 1990). Pharmacokinetics Pharmacokinetics, toxicity and dosimetry have been previously reported (Epenetos et al, 1987;Stewart et al, 1989Stewart et al, , 1990Maraveyas et al, 1993).…”

“…The administered dose of radioactivity was measured in a SIEL isotope calibration chamber that had been calibrated with an yttrium-90 source (Stewart et al, 1990). Pharmacokinetics Pharmacokinetics, toxicity and dosimetry have been previously reported (Epenetos et al, 1987;Stewart et al, 1989Stewart et al, , 1990Maraveyas et al, 1993). Approximately 30% of the intraperitoneally injected immunoconjugate was absorbed into the systemic circulation by 48 h after administration (Stewart et al, 1989(Stewart et al, , 1990Maraveyas et al, 1993).…”

Prostate-specific membrane antigen (FOLH1): recent advances in characterising this putative prostate cancer gene

“…The complex is then excreted in the urine, resulting in reduced marrow toxicity. 46 Therefore, to date the results of anti-PSM/FOLH1 immunotherapy remain inconclusive and it is dif®cult to predict the eventual clinical value of 90 Y Cyt-356 at this stage.…”

Patients receiving murine monoclonal antibody therapy for malignancy develop T cells that proliferate in vitro in response to these antibodies as antigens

“…Murine monoclonal antibodies (MAbs) raised against tumourassociated antigens have been used in diagnostic (Mach et al, 1981;Epenetos et al, 1982;Oldham et al, 1984;Siccardi et al, 1989) and therapeutic trials (Dillman et al, 1983;Carrasquillo et al, 1984;Epenetos et al, 1987;Stewart et al, 1990). A major limitation of murine MAbs is the development of human anti-murine immunoglobuilin antibody (HAMA) responses (Schroff et al, 1985;Courtenay-Luck et al, 1986).…”