Chemotherapy in gastrointestinal malignancies

The frequency of gastrointestinal (GI) cancers mandates innovative and individualized therapies. Chemotherapy used as sole treatment for these diverse malignancies has not been generally successful in providing palliation or improving patient survival. Radiotherapy has been more successful at controlling local manifestations of disease, but the high incidence of systemic metastases in most malignancies limits the impact of this modality on curability. Combinations of radiotherapy and chemotherapy may prove to be more valuable than single modality treatment in improving local control of tumors, decreasing systemic disease, and improving patient tolerance to treatment. A model for this approach is the current management of anal cancer, in which combined modality therapy has largely supplanted primary surgery. Data from trials in other primary tumor sites strongly suggest further exploration of combined treatments--surgical, radiotherapeutic, and chemotherapeutic--in GI malignancies. Nearly 25% of all malignancies diagnosed in the United States each year involve the GI tract; thus, there is a powerful imperative for the development of new therapeutic strategies in these diseases. Any discussion of the role of chemotherapy in GI cancers must necessarily be broad, because assessment must include diseases with highly variable surgical curability, histologies, and sensitivities to chemotherapeutic agents. In addition, whereas it has been quite easy to perform standard phase II trials in colorectal cancer, other disease sites, such as the esophagus, the pancreas, and the biliary tract, have been much less extensively studied. In spite of these limitations, there is a wealth of data in the literature concerning the use of chemotherapy in GI malignancies. This article, while not exhaustive, describes the current status of chemotherapy for these diverse diseases, with emphasis on the role of mitomycin C.