Early Results of Combined Radiation and Chemotherapy in Treatment of Malignant Tumors

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Abstract
The knowledge of the effectiveness of adequately administered radiation therapy in achieving palliation and regression of certain types of malignant tumors and recent reports suggesting at least some effectiveness with the systemic use of chemotherapeutic agents in similar cases (1, 10) have precipitated an interest in the possibility of increasing therapeutic effectiveness by the use of these two modalities in combination. Published reports of such combined therapy have suggested an increased tumor response as compared to either method alone (4, 5, 8). In this series of cases treated with combined radiation and chemotherapy the results will be on the basis of patient survival; or in those instances where the patient is still alive, on objective evidence of tumor response. Because of the inherent dangers of the two therapy modalities, we are aware that premature conclusions can prove harmful in the long run. Case Selection This report is based on 99 cases of solid tumors. No patients with a diagnosis of leukemia or lymphoma were included. The diagnosis in all except 4 was advanced neoplasm, with definitive pathologic verification. In the majority other therapeutic regimes had been previously attempted, sometimes on several occasions. In none was the disease considered curable by accepted technics. Therapy Plan and Dosage The antimetabolite, 5-fluorouracil (5-FU), was the drug of primary interest in this series, although several patients received Actinomycin-D, Mitomycin-C, or Leukoran. The radiation employed was either orthovoltage or telecobalt 60, the technic being essentially that which would have been used for therapy without the drug. The total tumor dose of radiation was usually slightly less than if it had been the only treatment method and varied, depending upon the reaction of the individual patient. The 5-FU was administered by undiluted intravenous injection, although it was realized that delayed dilute intravenous infusion of the drug substantially reduces the incidence of toxic reactions (9). The undiluted method was selected because we attempted to treat all our patients as outpatients and also because in our observation of former patients treated with 5-FU alone, the desired tumor remission was not seen in those who did not receive sufficient amounts to reach toxicity levels (10). The 5-FU dosage schedule consisted of a daily injection of 15 mg. per kilogram of body weight for a total of three to five doses. The maximum dosage given was 1.0 gm. of drug in any one day. This was followed by a maintenance dose schedule, usually 7.5 mg. per kilogram of body weight once or twice weekly, depending upon patient response. Because of severe toxic reactions on this schedule, the initial drug-loading injections were reduced in some patients to 7.5 mg. per kilogram of body weight, followed by the described maintenance regime.

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