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Evaluation of Combination Chemotherapy in Vivo and in Culture with 1-ß-D-Arabinofuranosylcytosine and 1-Formylisoquinoline Thiosemicarbazone¹

Department of Experimental Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203

Combinations of 1-ß-D-arabinofuranosylcytosine and 1-formylisoquinoline thiosemicarbazone resulted in synergistic effects against leukemia L1210 in DBA/2Ha-DD mice. Data obtained in irradiated DBA/2Ha-DD mice, in DBA/2J mice, and in cell cultures indicated that these combinations actually have only additive inhibitory effects against the leukemia L1210 cells. These results indicate that a drug combination with only additive inhibitory effects on tumor cell growth can cause therapeutic synergism in vivo due to the participation of host defenses directed against the tumor.

¹ This investigation was supported in part by USPHS Research Grant CA-11047. The work reported herein was submitted by G. B. Grindey in partial fulfillment of the requirements for the Ph.D. degree in a cooperative program between the Program of Pharmacology, Roswell Park Memorial Institute, Division of the Graduate School, and the Department of Pharmacology, School of Medicine, State University of New York at Buffalo. A graduate fellowship from the New York State Department of Health supported G. B. Grindey.

² Present address: Wellcome Research Laboratories, 3030 Cornwallis Road, Research Triangle Park, N. C. 27709.

Received 7/13/71. Accepted 12/ 3/71.

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