Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies.

Abstract

Twenty-four patients with persistent epithelial ovarian cancer after chemotherapy with or without external beam irradiation, were treated with intraperitoneally administered 131I-labeled monoclonal antibodies HMFG1, HMFG2, AUA1, H17E2, directed against tumor-associated antigens. Acute side effects were mild abdominal pain, pyrexia, diarrhea, and moderate reversible pancytopenia. One patient developed a subphrenic abscess requiring surgical drainage. Eight patients with large volume disease, ie, greater than 2 cm tumor diameter, did not respond to antibody-guided irradiation and died of progressive disease within 9 months of treatment. Sixteen patients had small-volume (less than 2 cm) disease at the time of treatment with radiolabeled antibody. Seven patients failed to respond, and of nine initial responders, four patients remain alive and free from disease 6 months to 3 years from treatment. Analysis of the data on relapse indicated that doses greater than 140 mCi were more effective than lower doses. We conclude that the intraperitoneal administration of 140 mCi or more of 131I-labeled tumor-associated monoclonal antibodies represents a new and potentially effective form of therapy for patients with small-volume stage III ovarian cancer.

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

“…It was also found that treated patients developed anti-DOTA (Kosmas et al, 1990) and anti-CITC-DTPA antibodies. All patients developed human antimouse antibodies as previously reported (Epenetos et al, 1987;Stewart et al, 1989). The difference in toxicity and immunogenicity between DTPA and DOTA linkage between antibody and radionuclide as well as the HAMA levels are reported elsewhere (Kosmas et al, 1992;Maraveyas 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).…”

“…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). …”

Immunolocalisation and imaging of small cell cancer xenografts by the IgG2a monoclonal antibody SWA11

“…The use of monoclonal antibodies (MAbs) for diagnosis (Cuttitta et al, 1984), imaging (Mach et al, 1981;Smedley et al, 1983) and now therapy (Lobuglio et al, 1986;Epenetos et al, 1987) of malignant disease is an increasingly realistic objective. MAbs generated against surface antigens of SCC can be divided according to the nature and expression of their target antigens into five main clusters, as defined at the International Workshop on SCC, London 1987 (Souhami et al, 1988).…”

Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for the treatment of central nervous system malignancies

“…A further problem associated with the use of MAbs in patients compared with animals is the difference in the volume of distribution of the radioimmunoconjugate, potentially reducing the ability of MAbs to target to tumour. To attempt to overcome these problems several groups have concentrated their efforts on administering antibodies into body compartments that contain relatively small amounts of diffuse tumour (Epenetos et al, 1987;Lashford et al, 1988).…”