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October 1957

Use of Triethylene Thiophosphoramide (Thio-TEPA) in Treatment of Advanced Cancer

Author Affiliations

From the Departments of Surgery, Veterans' Administration Research Hospital, Chicago; Evanston Hospital, Evanston, Ill., and Northwestern University Medical School, Chicago.

AMA Arch Surg. 1957;75(4):615-624. doi:10.1001/archsurg.1957.01280160125016

N,N′,N″-triethylene thiophosphoramide (Thio-TEPA) belongs to the poly functioning alkylating group of compounds and is closely related pharmacologically to mechlorethamine hydrochloride U. S. P. (nitrogen mustard).10 It has proved effective in the treatment of certain chronic leukemias and lymphomas.10,15 In addition, tumors originating in the breast, ovary, and lung have occasionally responded favorably.1-4,9,14 This report deals with the use of triethylene thiophosphoramide in the attempted palliation of 34 patients with advanced neoplastic disease arising from tissues outside the hematopoietic system.

The mechanism of action of triethylene thiophosphoramide depends on the release of ethylenimine derivatives. These products, when dissolved in tissue fluids, are capable of alkylating a wide variety of organic compounds, including functioning groups of cell proteins. The most likely site of intracellular attack appears to be essential nucleoproteins of cell nuclei.14

The drug was supplied as a white crystalline powder and was prepared for use in