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CI-973, a New Platinum Derivative with Potential Antileukemic Activity¹

Departments of Hematology [S. O., H. K., E. F., K. N., M. B.] and Biomathematics [D. J.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

We examined the effects of CI-973 (supplied by Parke-Davis) on several human leukemia cell lines and a Chinese hamster ovary (CHO) line and their drug-resistant counterparts. The cell lines used were HL-60, HL-60/mAMSA, HL-60/DOX, KBM3, KBM3/mAMSA 6, KBM3/mAMSA 6(85), CHO, and CHO/AC-7. DOX, mAMSA, and AC-7 indicate resistance to doxorubicin, amsacrine, or 1-ß-D-arabinofuranosylcytosine, respectively. Cells were incubated with CI-973, and the effect was evaluated by two methods: growth inhibition assay and inhibition of colony formation.

All cell lines examined were inhibited by CI-973; two of three amsacrine-resistant lines and the one cytarabine-resistant line demonstrated collateral sensitivity. At equivalent dosages, a 4-day exposure provided much greater cell kill than a 1-h exposure. Clonogenic assay showed exponential killing over 3 log units. Maximum CI-973 levels required to kill 50% of cells were 10-fold lower than the peak plasma levels achieved in a phase I solid tumor study. A continuous infusion phase I study in acute leukemia has been initiated.

¹ This work was supported in part by Therapy and the Biology of Human Leukemia Grant CA39809.

² To whom requests for reprints should be addressed, at Department of Hematology, Box 61, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

Received 2/ 7/92. Accepted 5/13/92.