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Clinical Trial
. 2009 Apr 15;15(8):2935-41.
doi: 10.1158/1078-0432.CCR-08-2213. Epub 2009 Apr 7.

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

Stephen Shibata  1 , Andrew Raubitschek, Lucille Leong, Marianna Koczywas, Lawrence Williams, Jiping Zhan, Jeffrey Y C Wong
Affiliations
Clinical Trial

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

Stephen Shibata et al. Clin Cancer Res. .

Abstract

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.

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Figures

Fig. 1
Fig. 1
Y-90 dose (rad/mCi) to individual tumors compared with the volume of the individual tumors.
See this image and copyright information in PMC

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