[Antitumor effects of Behenoyl-ara-C (BH-AC) in combination with Idarubicin (IDA) in P 388 leukemic cell bearing mice].

Abstract

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.

• Authors: A Watanabe, H Kuriyama, T Kiyota
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 23 Issue 3 Pg. 291-6 (Feb 1996) ISSN: 0385-0684 [Print] Japan
• PMID: 8712821 (Publication Type: Comparative Study, English Abstract, Journal Article)

Chemical References

• Cytarabine
• enocitabine
• Idarubicin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Cytarabine (administration & dosage, analogs & derivatives)
• Drug Screening Assays, Antitumor
• Female
• Idarubicin (administration & dosage)
• Leukemia P388 (drug therapy, pathology)
• Mice
• Neoplasm Transplantation
• Tumor Cells, Cultured (drug effects, pathology)