Comparison of the cardiotoxic effects of liposomal doxorubicin (TLC D-99) versus free doxorubicin in beagle dogs.
The cardiotoxic potential of liposome encapsulated doxorubicin (TLC D-99) prepared by a remote-loading technique was compared with that of free doxorubicin (1.5mg/kg administered every 3 weeks for 8 cycles) in beagle dogs. Both agents were equally myelosuppressive, and all dogs completed both treatments. There were no deaths during the study. Experimental animals were killed between 157 and 164 days after the start of the trial. All of the dogs (n = 6) that received free doxorubicin had either moderate (1 animal) or severe (5 animals) vacuolization of myocardial tissue. None of the dogs treated with liposomal doxorubicin had lesions suggestive of cardiomyopathy. Administration of free doxorubicin was associated with transient anorexia, reduced weight gain, alopecia, and gastrointestinal toxicity. Such adverse reactions were either much less severe or absent in animals that received liposomal doxorubicin. The results of this study demonstrate that TLC D-99 significantly decreases both the myocardial toxicity and other adverse reactions of this potent antineoplastic drug. TLC D-99 is now in Phase II clinical trials.
James T. Grace Jr. Cancer Drug Center, Roswell Park Cancer Institute, New York State Department of Health, Buffalo 14263.
P M
PM
Kanter
G A
GA
Bullard
R A
RA
Ginsberg
F G
FG
Pilkiewicz
L D
LD
Mayer
P R
PR
Cullis
Z P
ZP
Pavelic
D000818:Animals; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004337:Drug Carriers; D005260:Female; D006321:Heart / Q000187:drug effects*; D006403:Hematologic Tests; D008081:Liposomes; D008297:Male
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin