cardiovascular-agents and Leukemia--Myeloid

The effects of adenosine, aminophylline, dipyridamole and salbutamol on the amine oxidase-mediated spermine cytotoxicity to KS62 human myelogenous leukemia cells without Ph-chromosome, spontaneously enriched with mildly adherent cells, were studied. In the absence of spermine, adenosine expressed very mild inhibitory action on K562 cell survival, while in combination with the polyamine an almost additive increase in spermine-FBS cytotoxicity was observed. Aminophylline and salbutamol attenuated both spermine-FBS and spermine-FBS-adenosine suppression of cell survival and viability when equimolar concentration of these agents and the adenosine were applied. Pre-treatment of the cells with higher adenosine levels, in the presence of either aminophylline or dipyridamole, or salbutamol, was associated with decreased K562 cell survival, with the appearance of morphological changes in 10-20% of cells. Additional spermine-FBS cytotoxic effect was not observed in cells pre-treated with adenosine-aminophylline, or adenosine-salbutamole, but morphological changes in 10-20% of cells, even in the presence of spermine, was observed again. Dipyridamole alone suppressed very weakly K562 cell survival. In cells pretreated with dipyridamole, in the presence of spermine-FBS, an additive decrease in cell survival was observed. Pre-treatment of cells with dipyridamole and adenosine in presence of spermine-FBS did not result in a decrease of cell survival compared to the one obtained in dipyridamole-spermine-FBS treated cells.

Topics: Adenosine; Adrenergic beta-Agonists; Albuterol; Aminophylline; Cardiotonic Agents; Cardiovascular Agents; Cell Survival; Dipyridamole; Drug Synergism; Humans; Leukemia, Myeloid; Oxidoreductases Acting on CH-NH Group Donors; Spermine; Tumor Cells, Cultured; Vasodilator Agents

The clinical use of anthracyclines and related antitumor agents is limited by their cumulative dose-related cardiac toxicity. Cardioxane (ICRF-187) is an agent that has been recommended to block selectively this toxicity which e.g. limits the use of daunorubicin (DNR) in doses higher than 550-700 mg/m2. We decided to use cardioxane in patients with relapsed acute myeloid leukemias (AML) who have previously been treated with DNR doses above 500 mg/m2. Seven patients with relapsed AML received cardioxane 30 min before DNR or mitozantrone (MTZ) in doses 8-13x higher than DNR or 40-60x higher than MTZ. Two patients received anthracyclines cumulative doses corresponding to more than 1300 mg/m2 and 1000 mg/m2 of DNR, respectively, without any signs of cardiac toxicity. The other 5AML patients in relapse received 1-3 chemotherapy cycles with cardioxane. Their total cumulative doses of DNR were 550-750 mg/m2 and their left ventricular ejection fraction remained above 50% as were their pretreatment values. Cardioxane seems to be a useful cardioprotective agent in relapsed AML which enables further treatment with anthracyclines.

Topics: Acute Disease; Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiovascular Agents; Cytarabine; Daunorubicin; Female; Heart; Humans; Leukemia, Myeloid; Male; Middle Aged; Razoxane; Recurrence