Chemoresponsiveness of Moloney sarcoma virus-induced osteosarcoma to adriamycin in the rat.

The Chemoresponsiveness of a Moloney sarcoma virusinduced osteosarcoma in the rat to i.v. Adriamycin ther apy was demonstrated by (a) prolongation of life span, (b) reduction in tumor size, and (c) morphological alterations of the neoplasm. Adriamycin was given to groups of osteosarcoma-bearing rats i.v. or i.p. at 2 mg/kg/week for 10 weeks, at 1 mg/kg/week for 10 weeks, and at 1 mg/kg on Monday, Wednesday, and Friday followed by a week of rest (repeated to a total of 10 injections). Rats receiving 1 mg/kg/week had the most consistent response to Adria mycin treatment, with a significant prolongation of life span from 40 through 95 days and a significant decrease in tumor diameter from 7 days through 50 days after the start of treatment. Other Adriamycin regimens also pro duced a significant increase in life span and a reduction in tumor size, compared to results with rats in the placebo group. Radiographie evaluation of osteosarcomas dem onstrated an increased radiodensity with Adriamycin ther apy, compared to a rapid proliferation and destruction of preexisting bone in the placebo group. Microscopic and ultrastructural evaluation of osteosarcomas following var ious intervals of Adriamycin revealed necrosis of tumor cells, fibroblastic proliferation, and mineralization of osteoid matrix. Metastatic lesions in lung and sublumbar lymph node also were sensitive to Adriamycin therapy, as reflected by necrosis of tumor cells. Evidence of conges tive heart failure and cardiomyopathy was observed in all groups of rats on Adriamycin chemotherapy. The sen sitivity of the osteosarcoma-bearing New Zealand black rat to the antitumor and cardiomyopathic effects of Adria mycin provides an animal system for evaluation of the oncolytic activity of new analogs as well as their cardi-