Intraperitoneal Therapy of Ovarian Cancer with Radiolabeled Monoclonal Antibodies
Intravenously administered radiolabeled tumor associated monoclonal antibodies can achieve successful imaging of tumor masses. However, the absolute amount of radiolabel reaching the tumor is disappointingly small and cannot, at present, be used therapeutically for most epithelial origin cancers although some encouraging exceptions have been reported.
One manoeuvre that has met with some apparent success is that of intracavity administration of labeled antibodies. The rationale here is that if intravenous administration of the antibodies leads to too small an uptake due to dilution, dissociation and catabolism, then direct placing of the antibody into a body region may enhance its chances of reaching the target. This form of therapy has been applied to the peritoneum for the treatment of ovarian cancer and to the pleural and pericardial cavities for the treatment of malignant serous effusions. Pharmacokinetic studies have shown that there is an exploitable concentration difference between the peritoneum and the plasma for many anti-neoplastic agents and furthermore, that macromolecules such as antibodies can penetrate deeper into tissues than conventional chemotherapy agents of smaller molecular weight. Using an experimental model (nude mice with intraperitoneally implanted human xenograft), it was shown that we could achieve a fifty-fold increase and faster localization of intraperitoneally administered antibody as compared to intravenous administration.
A Phase I clinical trial of intraperitoneally administered I-131 labeled tumor associated monoclonal antibodies was conducted in 12 patients with advanced ovarian cancer resistant to chemotherapy and/or abdominal radiotherapy. Toxicity was noted at a level of 100 mCi in patients with malignant ascites, and 150 mCi in patients without ascites. Diarrhoea and cytopenia were more marked in patients who had previously received abdominal radiotherapy. Three out of four patients with Stage IV and large volume disease (> 2 cm diameter) benefited symptomatically but died of their disease three to six months after treatment. Two patients with Stage III and large volume disease (> 2 cm diameter) had stable disease at six and eight months after treatment. Four out of six patients with Stage III and small volume (< 2 cm diameter) achieved complete remission for 3-24 months after treatment. Two out of these patients had positive washings as the only evidence of disease and they remain in remission for more than two years after therapy.
A Phase II double blind randomized clinical trial has recently commenced to examine these effects on a large number of patients and to define the mode of action of this method.
KeywordsOvarian Cancer Minimal Residual Disease Advanced Ovarian Cancer Malignant Ascites Abdominal Radiotherapy
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