Murray J L, Macey D J, Kasi L P, Rieger P, Cunningham J, Bhadkamkar V, Zhang H Z, Schlom J, Rosenblum M G, Podoloff D A
University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer. 1994 Feb 1;73(3 Suppl):1057-66. doi: 10.1002/1097-0142(19940201)73:3+<1057::aid-cncr2820731345>3.0.co;2-3.
Radiolabeled CC49, a second generation high affinity monoclonal antibody (MoAb) reactive with tumor-associated glycoprotein 72 (TAG72) has undergone previous Phase I testing in patients with colon cancer. Based on this report, the authors treated 15 refractory metastatic colon cancer patients with 131I-CC49 to determine its overall toxicity and the response to therapy of patients treated with it.
Patients received 75 mCi/m2 131I-CC49 (20 mg MoAb) intravenously for a period of 30-60 minutes. Whole body retention was derived from the measured dose-rate of I-131 monitored daily at 1 m using an ion chamber. Two whole-body and static-gamma camera images were taken of patients on days 4 and 7 after the infusion.
Nonhematologic toxicity (Grade 1-2) consisted of nausea (two patients), arthralgias (three patients), transient fever and chills (two patients), and transient blood pressure changes (two patients). At 4-5 weeks posttreatment, reversible Grade 3-4 thrombocytopenia was observed in 7 of 15 patients, and reversible Grade 3-4 granulocytopenia was observed in 6 of 15 patients. Twelve of 13 patients tested developed human anti-mouse antibody (range, 161 to > 20,000 ng/ml) at 6-8 weeks postinfusion. Mean +/- SD whole-body half-life (whole-body retention) of 131I-CC49 was 57.3 +/- 13.4 hours. Tumors were seen in all patients. In two of three patients treated a second time, an increased whole body clearance rate correlated with elevated human anti-mouse antibody, reduced uptake in tumor, and enhanced uptake in the thyroid. Estimated tumor doses ranged from 19-667 rads. Red marrow dose estimated from whole body retention ranged from 60 to 117 rads and correlated with decreases in platelet count. No objective tumor responses (i.e., partial or complete) were observed.
Despite minimal toxicity and favorable tumor uptake, efficacy has been limited at this dose and schedule.
