The objective of this Interactive R01 (I-R01) submitted in response to the RFA: CA-92-25 is to improve the longterm survival of patients with colorectal cancer metastatic to the liver and to avoid inappropriate treatment programs. This will be accomplished by collaboration amongst the clinical chemotherapy trials (Kemeny I-R01, IRPG Coordinator), studies of drug resistance (Bertino I-R01), and our Studies. The overall goal of this application is to utilize a monoclonal antibody strategy for more accurate Staging by the detection of occult metastatic cancer in patients with clinically isolated hepatic metastases entered into programs under the Kemeny I-R01 clinical trials. We will also obtain operative specimens from this patient population for laboratory study under the Bertino I-R01. Our program will focus on the utilization of the monoclonal antibody A- 33, developed at our institution. The associated antigen is a large molecular weight cell surface glycoprotein that is not secreted into the bloodstream, and the antibody is rapidly internalized after complexing. The patients have clinically isolated hepatic metastases undergoing surgery for hepatic resection or for hepatic artery pump placement for unresectable disease (Kemeny I-R01). Our projects include (1) the detection of occult bone marrow metastases, (2) intraoperative radioimmunodetection with a gamma detecting probe and an innovative intraoperative gamma camera, (3) immunobiological specificity of MAB nodal uptake, and (4) studies with murine IgG and humanized IgG/fragments. The failure to detect occult bone marrow or intra- abdominal extrahepatic metastatic cancer should maximize long-term survival of patients undergoing hepatic resection of hepatic artery chemotherapy. The positive detection of occult extrahepatic disease will avoid inappropriate treatment in such patients.
