We have treated 14
cancer patients with
liposome-encapsulated
doxorubicin (LED) at doses of 30, 45, 60, and 90 mg/m2.
Nausea and
vomiting,
phlebitis, and
stomatitis were minimal or absent at each dose, but dose-limiting
granulocytopenia occurred at 90 mg/m2.
Thrombocytopenia and/or
anemia also occurred in all patients treated at 60 or 90 mg/m2. Complete
alopecia was seen in one of three cases at 60 mg/m2 and all cases at 90 mg/m2. No hepatic, renal, or other major organ toxicities were encountered. Clinical
cardiac toxicity did not occur in any patient, but the cumulative
doxorubicin doses in 13 cases were less than 400 mg/m2. The plasma elimination of LED out to 24 hours was analyzed in terms of a two-compartment model. Depending upon the dose and the infusion time, maximum plasma concentrations ranged from 2.6 mumol/L to 36.89 mumol/L and the area under the plasma concentration x time curve (AUC) values ranged from 1.86 mumol/L x h/L to 49.57 mumol x h/L. These values are significantly higher than those expected for free
doxorubicin. Urinary excretion of LED was approximately 10% after 24 hours.
Doxorubicinol and
doxorubicinone appeared at low levels in plasma 12 to 24 hours after injection. LED pharmacokinetics differ from those of free
drug by the higher plasma levels and AUC of
doxorubicin achieved, and by the low conversion of LED to metabolites. Overall, LED was well tolerated and produced only moderate
nausea and
vomiting and little
stomatitis at myelosuppressive doses. The study also suggested that LED produces less venous
sclerosis than free
doxorubicin, but this requires further clinical verification.