Phase I radioimmunotherapy trial with iodine-131-CC49 in metastatic colon carcinoma

CC49is a munnemonodonalantibody(MAb)that reactsagainst the TAG-72antigen.We carriedout a Phase I studywfthesca latingdoses of 131I..@49in patientswithadvanced colorectaJ cancer expressingthe TAG-72antigento determinethe dose Iimrnng todcftyand therapeudcefficacy,ifany,ofthe radioimmu noconjugate.Methods: Twenty-four patientswfthTAG-72-ex @rig colorectalcancerweretreatedw@escalatingdoses of 131I@49 starting at 15 mCVm@ and going up to 90 mCVm@ of 1311labeled to 20 mg MAb CC49. Patients were Selected it TAG-72was expressed in 50%ofcells in previouslyresected tumorand at least one metastasis was demonstrableon stan dard imagingsuch as CT.Allpatients had failedconventional chemotherapyand hed notreceivedpriorradiotherapy or munne MAb.Patients were under rediationisolationprecautionsuntil whole-bodyredioactMty decreased to 5 mR/hrat 1 m.Whole bodyscintigramswere obtainedpriorto dischargeand 1 and 2 wkafterinfusion inallpatients. SPECTimaging wascarried out at least once in all patients.Results: a@Jl patientshed excellent targetingof radioactivity to knowntumor sites. There was no nonhematologictoxicity.HernatOIOgIC todcity was more pro nounced in those patients who had received extensive prior chemotherapy.There were no major responses. PJI patients developedan immuneresponse (HAMA) within4 wkoftherapy. Conclusion: Rad,oimunotherapy with131l@49 is safe and there ussignificant therapeuticefficacyinthis Phase Itrialat the doses studied. There is excellenttargeting of radioactivity to antigen-positive tumors. Dose-limiting toxicityis hematopoietic, w@1 themadmum tolerated doseinthisgroup ofhea@ pre treated patientsbaing75 mCWm@.