Eight adults and five children with various types of far-advanced cancer were treated with repeated doses of 0.2 to 4.0 mg/kg of 2-amino-4′,4″-bis(4-methyl-2-imidazolin-2-yl)-terephthalanilide (NSC 66761) (AMIT). Five adults and four children, considered to have received adequate trials, did not show any evidence of therapeutic benefit. Toxic symptoms included acute cholinergic reactions, anorexia, weakness, light-headedness, headache, blurred vision, obtundation, hematopoietic depression, abnormalities in renal function, and electrolyte disturbances.

Blood levels and excretion studies indicated that the blood level of AMIT fell rapidly after a single dose was injected intravenously and the half-life of AMIT in the blood was about 30 minutes. Repeated dosage caused a cumulative rise in the blood level. Urine excretion after a single injection was low, amounting to 17.9% and 14.1% of the injected amount over 96 hours. The amount of AMIT in the liver, kidney, brain, and cancer tissue was determined 31 and 44 days after the completion of a series of intravenous injections. Of the total amount administered, 3.8% and 4.2% was found in the liver and 0.85% and 0.51% in the kidneys. Cancer tissue contained only about half the concentration found in the liver. The brain contained a negligible amount.

1

These studies were supported in part by Grants CA-08748 and CA-05826 from the National Cancer Institute, NIH, USPHS.

2

Reprint requests to Dr. I. H. Krakoff, Sloan-Kettering Institute, 410 E. 68th St., New York, N. Y. 10021.

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