The dosing schedule dependent toxicities of adriamycin in beagle dogs and rhesus monkeys

The toxic effects of Adriamycin were studied following i.v. administration of from 10.0 mg/kg to 0.039 mg/kg (200--0.780 mg/m2) to beagle dogs, and from 5.83 mg/kg to 0.625 mg/kg (49.9--7.5 mg/m2) in rhesus monkeys by a variety of short and long term treatment schedules. 5 daily doses and 1 dose every 3 weeks were given for both species and, only in dogs, as single injections, 10 daily treatments and 5 daily doses followed by 9 days rest, repeated 3 times. In both species, short term administration of toxic doses caused weight losses, anorexia, diarrhea, atypical oesophageal and intestinal mucosa, bone marrow hypoplasia, lymphoid atrophy and alopecia. Specific adverse responses seen only in monkeys were hypocalcemia, hypomagnesemia, atypical buccal mucosa and reddish urinary pigmentation. Testicular degeneration and prostatic atrophy were produced in dogs. The triweekly treatment schedule caused an additional toxicity at lower doses. In both species a cardiotoxicity syndrome developed with pulmonary oedema and centrolobular hepatic necrosis, plus focal necrosis and vacuolization in cardiac myocytes. Clinical signs of cardiac dysfunction were EKG arrhythmias in dogs, and peripheral oedema, ascites and hydrothorax in monkeys.