[Antitumor effects of Behenoyl-ara-C (BH-AC) in combination with Idarubicin (IDA) in P 388 leukemic cell bearing mice].
The antitumor effects of Behenoyl-ara-C (BH-AC) in combination with Idarubicin (IDA) on leukemia were studied. First, a combination of IDA with Ara-C, which is the main metabolite of BH-AC, was evaluated with regard to its in vitro cytotoxic activity on mouse P 388 leukemic cells. The effect of this combination proved to be additive according to isobologram analysis. Secondly, the antitumor activity of an intravenous bolus-administration of a combination of BH-AC and IDA was evaluated by the life span of P 388 bearing mice, and compared with the activity of the Ara-C and IDA combination. The antitumor activity of Ara-C administered alone was clearly dependent on the administration schedule and was most intense when Ara-C was administered with the most frequent injections (3 bolus injections/day x 3 days), whereas antitumor activity of BH-AC was less dependent on the schedule. IDA administered alone showed dose-dependency in its antitumor activity up to 3 mg/kg. The maximum effects of IDA were observed with amounts of 3 - 4 mg/kg. In the same leukemia model, the combination of frequent injections of BH-AC and a single injection of IDA (increased life span: ILS>300%; cure ratio: CR = 3/5) conferred a more potent effect compared to the results of BH-AC (ILS = 133%, CR = 0/5) or IDA (ILS = 67%, CR = 2/5) alone. The effect of BH-AC and IDA combination was comparable or superior to that of the Ara-C and IDA (ILS = 233%, CR = 2/5) combination. These results indicated the possibility of clinical usefulness with a combination therapy of BH-AC and IDA against leukemia.
Watanabe
A
A
Laboratory for Immunology Institute for Life Science Research, Asahi Chemical Industry Company, Ltd., Japan.
Kuriyama
H
H
Kiyota
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015255:Idarubicin / Q000008:administration & dosage; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D003561:Cytarabine; C015019:enocitabine; D015255:Idarubicin