CI-973, a new platinum derivative with potential antileukemic activity.
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-beta-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.
O'Brien
S
S
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Kantarjian
H
H
Freireich
E
E
Johnston
D
D
Nguyen
K
K
Beran
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007938:Leukemia; D015473:Leukemia, Promyelocytic, Acute; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; C055425:NK 121; D016190:Carboplatin