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A Phase I Study of a Combination of Yttrium-90–Labeled Anti–Carcinoembryonic Antigen (CEA) Antibody and Gemcitabine in Patients with CEA-Producing Advanced Malignancies

Purpose: To determine the maximum tolerated dose of combined therapy using an yttrium-90–labeled anti–carcinoembryonic antigen (CEA) antibody with gemcitabine in patients with advanced CEA-producing solid tumors. Experimental Design: The chimeric human/murine cT84.66 is an anti-CEA intact IgG1, with high affinity and specificity to CEA. This was given at a fixed yttrium-90–labeled dose of 16.6 mCi/m2 to subjects who had and an elevated CEA in serum or in tumor by immunohistochemistry. Also required was a tumor that imaged with an 111In-labeled cT84.66 antibody. Patients were treated with escalating doses of gemcitabine given i.v. over 30 minutes on day 1 and 3 after the infusion of the yttrium-90–labeled antibody. Patients were treated in cohorts of 3. The maximum tolerated dose was determined as the highest level at which no >1 of 6 patients experienced a dose limiting toxicity. Results: A total of 36 patients were enrolled, and all but one had prior systemic therapy. The maximum tolerated dose of gemcitabine in this combination was 150 mg/m2. Dose limiting toxicities at a gemcitabine dose of 165 mg/m2 included a grade 3 rash and grade 4 neutropenia. One partial response was seen in a patient with colorectal cancer, and 4 patients had a >50% decrease in baseline CEA levels associated with stable disease. Human antichimeric antibody responses were the primary reason for stopping treatment in 12 patients. Conclusions: Feasibility of combining gemcitabine with an yttrium-90–labeled anti-CEA antibody is shown with preliminary evidence of clinical response.