Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial.
OBJECTIVE
Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS).


METHODS
Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes.


RESULTS
Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin.


CONCLUSIONS
Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.
University of California, San Francisco, USA. dnorthfelt@pol.net
D W
DW
Northfelt
B J
BJ
Dezube
J A
JA
Thommes
B J
BJ
Miller
M A
MA
Fischl
A
A
Friedman-Kien
L D
LD
Kaplan
C
C
Du Mond
R D
RD
Mamelok
D H
DH
Henry
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010592:Pharmaceutic Aids / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000821:virology*; D013501:Surface-Active Agents / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
D004337:Drug Carriers; D008081:Liposomes; D010592:Pharmaceutic Aids; D013501:Surface-Active Agents; D001761:Bleomycin; D011092:Polyethylene Glycols; D014747:Vinblastine; D004317:Doxorubicin