In cooperation with the Department of Nuclear Medicine, and the Laboratory of Tumor Immunology and Biology, we have initiated clinical trials for the treatment of peritoneal carcinomatosis. A classical phase one study has begun using escalating doses of 1-131 labeled antibody administered intraperitoneally. Since last year's report we have only treated an additional four patients as well as continue to follow the patients treated initially. We have now reached a dose of 150 mCi of Iodine-131 labeled b72.3. With the Increased doses we have noticed the appearance of two new symptom complexes. One we relate to a mild peritonitis occurring approximately one week after treatment and manifest by mild abdominal tenderness and the accumulation of ascites. These symptoms resolve spontaneously over the following few weeks requiring no medical intervention. We have also noticed the onset of diarrhea several days after-the administration of the isotope. This also resolves without treatment over a few weeks. This Is probably a direct effect of the radiation on the mucosal surface of the gastrointestinal track. Dose limiting toxicity appears still to be bone marrow, with patients with extensive previous chemotherapy being limited to 125-150 mCi. Patients without extensive pretreatment may be able to receive as high as 175 mCi, although this dose level has not been reached yet. The clinical protocol has been recently revised by Dr. Carrasquillo to more accurately define the maximum tolerated doses. A follow-up protocol using a higher affinity antibody CC49, with concomitant administration of intraperitoneal gamma interferon is being written.
