Effects of Intracarotid Administration of Nitrogen Mustard on Normal Brain and Brain Tumors

Abstract

T HE relative effectiveness of intravenous nitrogen mustard in the palliative treatment of neoplastic diseases has been extensively reported since the first clinical trials by Gilman and associates in 194r Such therapy was found to be of limited value, however, since experience showed that temporary regression occurred primarily in the malignant lymphomas and only occasionally in bronchogenic carcinoma. ~,l~ The great majority of neoplasms appeared to be resistant to the drug. Recently this concept has been altered by Bierman el al. 1,2,3,4 and Klopp et al2 who devised techniques for the administration of nitrogen mustard in high dosage directly to the tumor by way of its arterial blood supply and found even radio-resistant neoplasms to be responsive under these conditions. This approach is particularly applicable for chemotherapy of primary and secondary tumors of the liver, where the normal parenchyma has a double blood supply and the neoplasm only one, 1 thus permitting selective concentration of the drug in the lesion. While similar vascular anatomy is not found in the brain, the possibility of treating intracranial malignancies was suggested by reports of such regional therapy, since it was felt that the high resistance of nervous tissue to irradiation might permit administration of a radiomlmetic drug in sufficient dosage to damage the neoplasm without destroying normal brain. For this reason, experiments were performed in cats and monkeys to study the effect produced by the injection of HN: (methyl bis ~--chloroethyl amine) into the carotid artery on function and structure of the brain. These effects were correlated with those observed after similar injections in 3 patients suffering from primary or metastatic cerebral disease.