Treatment of Malignant Neoplasms of the Gastrointestinal Tract With a Combination of 5-Fluorouracil and Radiation

Combined chemotherapy and irradiation in the management of malignant disease is a subject of wide and current interest. It has been hoped that the combining of these therapeutic modalities would produce results superior to those achieved with either alone. Hodnett recently reviewed the literature in this field (4). Some authors believe that their results demonstrate marked synergism or additive effects of the combined therapy, while others have withheld judgment, pending the results of controlled studies. The University of Wisconsin group published several reports of controlled studies. They used 5-fluorouracil (5-FU) and irradiation to treat mammary carcinoma of mice (6) and the same combination for bronchogenic carcinoma in man (1, 3). In the animal studies, the combination of 5-fluorouracil, actinomycin P2, or cyclophosphamide (Cytoxan) with fractional x-ray therapy resulted in increased inhibition of tumor growth as well as in prolonged survival when compared to either mode of therapy alone. From their studies of bronchogenic carcinoma in man, they concluded that the data suggest a significant increase in the survival time after radiation therapy and 5-FU. They pointed out that the many variables in therapy, such as the ideal tumor dose and the mode of fractionation of the chemotherapeutic agent, require several controlled studies to determine whether combined therapy is superior to radiation or chemotherapy alone. Von Essen and his co-workers (7) reported a controlled study in which radiation and 5-fluorouracil were employed to treat a variety of tumors to determine the response to radiation alone and to radiation plus 5-FU. A method of interior control was used in the experimental plan. The study failed to demonstrate a significant alteration in tumor response by the addition of 5-FU to x irradiation. It is evident from the literature that one of the major difficulties of such controlled studies is in amassing sufficient cases to demonstrate statistically significant differences. Inoperable malignant tumors of the gastrointestinal tract represent a difficult problem for the cancer therapist. Although radiation therapy has occasionally achieved some measure of success in palliation of localized carcinoma, it has not played a major role in management. Therapy with the fluorinated pyrimidines, 5-fluorouracil (5-FU) and 5-fluoro-2-de-oxyuridine (5-FUDR), is sometimes capable of inducing a regression of gastrointestinal cancer. These observations raise the possibility that combined therapy could enhance the results achieved by either mode of therapy alone. A pilot study (5) was undertaken by the authors to determine (a) the dosage of 5-FU which would be relatively safe and tolerable in combination with supervoltage radiation, and (b) whether combined 5-FU and supervoltage irradiation were capable of producing useful palliation in a sufficient number of patients to justify further systematic evaluation.