Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma.
Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m(2)) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T(1)S(1)). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at (http://www.clinicaltrials.gov) as no. NCT00020449.
Little
Richard F
RF
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA.
Aleman
Karen
K
Kumar
Pallavi
P
Wyvill
Kathleen M
KM
Pluda
James M
JM
Read-Connole
Elizabeth
E
Wang
Victoria
V
Pittaluga
Stefania
S
Catanzaro
Andrew T
AT
Steinberg
Seth M
SM
Yarchoan
Robert
R
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D054357:Chemokine CXCL10 / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004359:Drug Therapy, Combination; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000633:toxicity; D012074:Remission Induction; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C506643:liposomal doxorubicin; D018664:Interleukin-12; D011092:Polyethylene Glycols; D004317:Doxorubicin; D007371:Interferon-gamma