Over the next five years of this Program Project we will continue to make strong efforts to bring together in a coordinated unit the clinical research disciplines and related laboratories of the Mayo Clinic for the purpose of improving both palliative and curative treatment of human gastrointestinal cancer. The following specific areas will be addressed: 1) Treatment of colorectal cancer. 2) Treatment of the less common gastrointestinal carcinomas and 3) Gastrointestinal Cancer Laboratory Science. We continue to place special emphasis on the development and testing of innovative approaches to regional disease and surgical adjuvant therapy with cure as a specific end point. Of primary importance will be the integration directly into clinical research programs of sophisticated laboratory endeavors in cancer pharmacology, cytogenetics and immunology. We will continue to utilize the particular strengths of this program which include an unexcelled depth of experience in gastrointestinal clinical cancer research; a devoted clinical research team including all concerned disciplines; the exceptionally large cancer patient population available at the Mayo Clinic permitting meaningful studies to be performed in a timely fashion; the uniquely large population of newly diagnosed gastrointestinal cancer permitting conduct of early disease studies; an extraordinarily large population of patients with less common cancers; strong relationships with community clinics in our region through the North Central Cancer Treatment Group permitting a continuum of management and expanded Phase III trials utilizing the same data base; a well developed Mayo Cancer Center Statistical Unit which is involved in all phases of our studies to insure sound protocol design, consistent data quality, and informed and objective data analysis; and ready availability of large amount of tissue and laboratory materials for basic laboratory study. We believe these ingredients combined with our established productivity and our documented accomplishment during the first two and one-half years of this grant provide maximum confidence that the work proposed will meet highest scientific standards and will be conducted with unexcelled quality and cost effectiveness.