Esophageal cancer and the esophagus: Challenges and potential strategies for selective cytoprotection of the tumor-bearing organ during cancer treatment

Esophageal cancer is treated optimally with a combined-modality approach according to most clinical investigators. Cytotoxic chemotherapy and ionizing radiotherapy, given in a concomitant schedule, has yielded superior survival rates compared with radiotherapy alone. However, mucosal toxicity from such treatment may compromise quality of life and may mandate an unscheduled break in therapy in some patients who do not respond readily to standard treatments such as antacids; combinations of viscous xylocaine, aluminum hydroxide-magnesium carbonate, and diphenhydramine hydrochloride; oral liquid morphine sulfate, hydrocodone bitartrate, or acetaminophen. Hence, a number of alternative strategies that are designed to either prevent or limit toxicity to normal tissues without diminishing the antitumor effect are being tested. These include the use of conformal radiotherapy treatment planning techniques, amifostine (Ethyol, WR-2721), gene therapy via intratumoral injection of manganese superoxide dismutase-plasmid/liposome, glutamine, melatonin, omega-3-polyunsaturated fatty acids, transforming growth factor, flavonoid compounds, probucol, and keratinizing growth factor. An ongoing phase 2 trial by the North Central Cancer Treatment Group (NCCTG) may help clarify a role for cytoprotectants in patients receiving combined-modality therapy for esophageal cancer.