The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin.
BACKGROUND
Pegylated liposomal doxorubicin (PL-DOX) has been shown in preclinical models to induce less cardiotoxicity than non-liposomal doxorubicin. Endomyocardial biopsy is a highly sensitive and specific method for detecting anthracycline-induced cardiac damage.


METHODS
Myocardial tissue from ten KS patients who had received cumulative PL-DOX (20 mg/m2/biweekly) of 440-840 mg/m2 was evaluated for evidence of anthracycline-induced cardiac damage. Controls were assembled from patients who had received cumulative doxorubicin doses of 174-671 mg/m2 in two earlier cardiac biopsy protocols. Two control groups were selected on the basis of both cumulative (+/- 10 mg/m2) and peak doxorubicin dose (60 or 20 mg/m2, control group 1), or peak dose alone (20 mg/m2, control group 2).


RESULTS
PL-DOX patients had significantly lower biopsy scores compared with those of doxorubicin controls despite higher cumulative doses of anthracycline. The median biopsy scores for the PL-DOX and doxorubicin groups, respectively, were 0.3 vs. 3.0 (P = 0.002, Cochran-Mantel-Haenszel row mean difference test) for group 1 and 1.25 for group 2 (P < 0.001, Wilcoxon rank-sum test).


CONCLUSIONS
Less severe cardiac changes were seen in patients given PL-DOX relative to historical control patients given comparable cumulative doses of doxorubicin.
Berry
G
G
Department of Surgical Pathology, Stanford University, CA, USA.
Billingham
M
M
Alderman
E
E
Richardson
P
P
Torti
F
F
Lum
B
B
Patek
A
A
Martin
F J
FJ
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001706:Biopsy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D004337:Drug Carriers; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy*; D018709:Statistics, Nonparametric
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin