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Effects of 2'-Deoxycoformycin, 9-ß-D-Arabinofuranosyladenine 5'-Phosphate, and 1-ß-D-Arabinofuranosylcytosine Triple Combination Therapy on Intracerebral Leukemia 1210

Department of Biophysical Sciences, University of Houston, Houston, Texas 77004

The triple combination of 2'-deoxycoformycin (2'-dCF), 9-ß-D-arabinofuranosyladenine 5'-phosphate, and 9-ß-D-arabinofuranosylcytosine was found to be very effective in the therapy of C57BL x DBA/2 F₁ mice with intracerebral L1210. At the dosages and dosage scheduling used, the double combination of 2'-dCF and 9-ß-D-arabinofuranosyladenine 5'-phosphate gave minimal but significant increases in life-span. When 9-ß-D-arabinofuranosylcytosine was given at suboptimal dosage to mice with intracerebral L1210, the host toxicity caused by 2'-dCF and 9-ß-D-arabinofuranosyladenine 5'-phosphate in combination was decreased by a factor of 2, allowing a more prolonged therapy. "Cures" were obtained with the triple combination at dosages of 9-ß-D-arabinofuranosylcytosine that did not "cure." The supernantant adenosine deaminase from C57BL x DBA/2 F₁ mouse brains was purified and the K₁ for 2'-dCF using 9-ß-D-arabinofuranosyladenine as substrate was determined to be not more than 2 x 10^–11 M.

¹ Present address: Department of Pharmacology, Yale University College of Medicine, New Haven, Conn.

² Supported by Grant CA 12327 from the National Cancer Institute, NIH, and Grant E-321 from the Robert A. Welch Foundation. To whom requests for reprints should be addressed.

Received 3/14/77. Accepted 6/13/77.