Ganglioneuropathy in rabbits and a rhesus monkey due to high cumulative doses of doxorubicin.

The effects of long-term administration of doxorubicin in adult rabbits and in a rhesus monkey were studied. Eleven rabbits were given cumulative doses of 2--24 mg/kg over a period of 5--28 weeks. The monkey received a total of 20 mg/kg during a 10-month period. One rabbit exhibited hind leg paresis, but all of the other animals in the study remained clinically free of neurologic signs. Rabbits given less than 12 mg/kg of doxorubicin had only mild degenerative changes in dorsal roots and a few necrotic neurons in the dorsal root ganglia, but these lesions were much more severe in all rabbits when a cumulative dose greater than 16 mg/kg was given. The monkey also had severe ganglioneuropathy, suggesting that primates may also be susceptible to this toxic effect of doxorubicin. Although neurotoxicity has not been observed with the dose schedules of doxorubicin used in clinical practice, the tendency of this drug to damage both postmitotic neural and cardiac cells may provide added understanding of the clinically important doxorubicin cardiomyopathy.