Clinical and pharmacologic studies with adriamycin-DNA complex in children with malignant disease

During the last 4 years, we have studied the adriamycin-DNA complex originally developed by Trouet and co-workers (1972). This paper summarizes the results of our pharmacologic and clinical studies. The complex is taken up by cells through an adsorptive pinocytosis, with DNA as the binding molecule. Excess DNA prevents uptake of the drug. Administration of the drug as the complex results in much higher serum concentration and a reduced urinary excretion. The complex is well tolerated, but side effects are probably of the same order as those seen with the free drug. An exception may be the heart. The acute toxicity is not seen when infusing the complex. Our experience with 20 children who have received more than 500 mg/m2 indicates that the chronic cardiac toxicity may be reduced, too. Spectacular, but anecdotal, results have been observed in a variety of solid tumors. Of 16 children with acute myelogenous leukemia, 14 went into a complete remission on a protocol of cytosine arabinoside in combination with the complex. Three of these children are now off therapy, with the longest observation period being 4 years and 4 months.