RESULTS OF A PHASE-I TRIAL OF A RECOMBINANT VACCINIA VIRUS THAT EXPRESSES CARCINOEMBRYONIC ANTIGEN IN PATIENTS WITH ADVANCED COLORECTAL-CANCER

Background: The inadequacy of systemic treatments of advanced colorect al cancer has aroused interest in biologic therapy. Recent animal mode ls have demonstrated the efficacy and safety of a recombinant vaccine that contains vaccinia and the gene for carcinoembryonic antigen (rV-C EA). Methods: A phase I clinical trial of rV-CEA was conducted to asse ss vaccine toxicities, the maximum tolerated dosage, resulting immune activities, and tumor responses. A dose-escalation protocol was devise d for three concentrations. Six patients per dosage were each to recei ve three vaccinations. Results: Seventeen patients with advanced color ectal cancer received a total of 44 vaccinations. Mild local and syste mic reactions-comparable to those seen with vaccinia alone-were observ ed and were typically associated with the first vaccination. No signif icant complications or deaths were caused by the rV-CEA. In particular , no autoimmune colitis developed, nor did leukopenia occur, despite s ome homology between CEA and leukocyte antigens. All three vaccine con centrations were equally well tolerated. Most patients demonstrated tu mor progression by clinical and radiographic parameters and by CEA lev els. Immune assays are pending. Conclusions: This phase I trial demons trated the safety of rV-CEA in patients with advanced colorectal cance r. Future clinical studies are warranted and will likely be influenced by investigations of the immune responses to the vaccine.