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/m(2) to subjects who had and an elevated CEA in serum or in tumor by immunohistochemistry. Also required was a tumor that imaged with an (111)In-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/m(2). Dose limiting toxicities at a gemcitabine dose of 165 mg/m(2) 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.